US5559110AExpiredUtility
Pharmaceutical formulations of cyclic urea type compounds
Est. expiryMar 9, 2014(expired)· nominal 20-yr term from priority
Inventors:Bruce J. Aungst
A61K 31/554A61K 31/551A61K 9/4858A61K 31/513
48
PatentIndex Score
16
Cited by
15
References
41
Claims
Abstract
Compositions comprising a cyclic urea type compound in a liquid or solid vehicle comprising a fatty acid ester of glycerol, or a fatty acid ester of polyethylene glycol, or a mixture thereof, wherein said vehicle has an hydrophil-lipophil balance of at least about 10, and, optionally, other excipients are described. The compositions are useful for providing good systemic absorption of the cyclic urea compounds when administered enterally, especially orally. The subject compounds and compositions are useful for treating viral infections, particularly HIV infection, in a mammal.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1. A pharmaceutical composition comprising: (a) a therapeutically effective amount of compound of the Formula (I): ##STR16## or a pharmaceutically acceptable salt or prodrug form thereof, wherein: R 4 and R 7 are independently selected from the following groups: hydrogen; C 1 -C 8 alkyl substituted with 0-3 R 11 ; C 2 -C 8 alkenyl substituted with 0-3 R 11 ; C 2 -C 8 alkynyl substituted with 0-3 R 11 ; a C 3 -C 14 carbocyclic ring system substituted with 0-3 R 11 or 0-3 R 12 ; a 5- to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-2 R 12 ; or --OR 13 ; --SR 13 ; CO 2 R 13 ; R 4A and R 7A are independently selected from the following groups: hydrogen; C 1 -C 4 alkyl substituted with 0-6 halogen or 0-3 C 1 -C 2 alkoxy; benzyl substituted with 0-6 halogen or 0-3 C 1 -C 2 alkoxy; or --OR 13 ; --SR 13 ; CO 2 R 13 ; R 4 and R 4A can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R 12 ; R 7 and R 7A can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R 12 ; n is 1; R 5 is selected from H; halogen; C 1 -C 6 alkyl substituted with 0-3 R 11 ; --N(R 20 2 ; --SR 20 ; or --OR 20 , --N 3 ; R 6 is independently selected from: hydrogen, halogen, C 1 -C 6 alkyl substituted with 0-3 R 11 , --N(R 20 ) 2 , --SR 20 , or --OR 21 , --N 3 ; R 5 and R 6 can alternatively join to form an epoxide or aziridine ring; --OCH 2 SCH 2 O--; --OS(═O)O--; --OC(═O)O--; --OCH 2 O--; --OC(═S)O--; --OC(═O)C(═O)O--; --OC(CH 3 ) 2 O--; --OC((CH 2 ) 3 NH 2 )(CH 3 )O--; --OC(OCH 3 ) (CH 2 CH 2 CH 3 )O--; --OS(═O)O--; --NHC(═O)NH--; --OC(═O)NH--; --NHC(═O)O--; --NHCH 2 O--; --OCH 2 NH--; --NHC(═S)O--; --OS(═O)NH--; --NHC(═O)C(═O)O--; --OC(═O)C(═O)NH--; --NHC(═O)C(═O)NH--; --OC(CH 3 ) 2 O--; --NHC(CH 3 ) 2 O--; --OC(CH 3 ) 2 NH-- or any group that, when administered to a mammalian subject, cleaves to form a free dihydroxyl or diamino or hydroxyl and amino; R 5a is selected from hydrogen, halogen, C 1 -C 6 alkyl, --N(R 20 ) 2 , --SR 20 , or --OR 20 ; R 6a is selected from: hydrogen, halogen, C 1 -C 6 alkyl, --N(R 20 ) 2 , --SR 20 or --OR 21 ; R 5 and R 5a can alternatively join to form ═O, ═S, or a ketal ring; R 6 and R 6a can alternatively join to form ═O, ═S, or a ketal ring; R 20 and R 21 are independently selected from: hydrogen; C 1 -C 6 alkyl substituted with 0-3 R 11 ; C 3 -C 6 alkoxyalkyl substituted with 0-3 R 11 ; C 1 -C 6 alkylcarbonyl substituted with 0-3 R 11 ; C 1 -C 6 alkoxycarbonyl substituted with 0-3 R 11 ; C 1 -C 6 alkylaminocarbonyl substituted with 0-3 R 11 ; benzoyl substituted with 0-3 R 12 ; phenoxycarbonyl substituted with 0-3 R 12 ; phenylaminocarbonyl substituted with 0-3 R 12 ; or any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl, amino or sulfhydryl; R 11 is selected from one or more of the following: H, keto, halogen, cyano, --CH 2 NR 13 R 14 , --NR 13 R 14 , --CO 2 R 13 , --OC(═O)R 13 , --O 13 , C 2 -C 6 alkoxyalkyl, --S(O)hd mR 13 , --NHC/(═NNH)NHR 13 , --C(═NH)NHR 13 , --C(═O)NR 13 R 14 , --NR 14 C(═O)R 13 , ═NOR 14 , --NR 14 C(═O)OR 14 , --OC(═O)NR 13 R 14 , --NR 13 C(═O)NR 13 R 14 , --NR 14 SO 2 NR 13 R 14 , --NR 14 SO 2 R 13 , --SO 2 NR 13 R 14 , --OP(O) (OR 13 ) 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 3 -C 10 cycloalkyl, C 3 -C 6 cycloalkylmethyl, benzyl, phenethyl, phenoxy, benzyloxy, nitro, C 7 -C 10 arylalkyl, hydroxamic acid, hydrazide, boronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, C 1 -C 4 alkyl substituted with --NR 13 R 14 , C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --OCH 2 CO 2 H, 2-(1-morpholino)ethoxy, azido, or --C(R 14 )═N(OR 14 ); - 3amino acids linked together via amide bonds, said amino acid being linked via the amine or carboxylate terminus; C 3 -C 10 cycloalkyl substituted with 0-2 R 12 ; C 1 -C 4 alkyl substitued with 0-2 R 12 aryl(C 1 -C 3 alkyl) substituted with 0-2 R 12 ; C 2 -C 6 alkoxyalkyl, substituted with 0-2 R 12 ; C 1 -C 4 alkylcarbonyloxy substituted with 0-2 R 12 , C 6 -C 10 arylcarbonyloxy substituted with 0-2 R 12 , a C 5 -C 14 carbocyclic residue substituted with 0-3 R 12 ; or a 5- to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-3 R 12 ; R 11A is selected from one or more of the following: H, keto, halogen, cyano, --CH 2 NH 2 , --NH 2 , --NHMe, --CO 2 H, --OC(═O) (C 1 -C 3 alkyl), --OH, C 2 -C 6 alkoxyalkyl, --C(═O)NH 2 , --OC(═O)NH 2 , --NHC(═O)NH 2 , --SO 2 NH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 3 -C 10 cycloalkyl, C 3 -C 6 cycloalkylmethyl, benzyl, phenethyl, phenoxy, benzyloxy, nitro, C 7 -C 10 arylalkyl, hydroxamic acid, hydrazide, boronic acid, C 3 -C 6 cycloalkoxy, C 1 -C 4 alkyl substituted with --NH 2 , C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --OCH 2 CO 2 H, 2-(1-morpholino)ethoxy, azido, aryl(C 1 -C 3 alkyl), a C 5 -C 14 carbocyclic residue; a 5- to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system substituted with 0-3 R 12 A; R 12 , when a substituent on carbon, is selected from one or more of the following: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, C 7 -C 10 arylalkyl, C 1 -C 4 alkoxy, --CO 2 H, hydroxamic acid, hydrazide, oronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, --OR 13 , C 1 -C 4 alkyl substituted with --NR 13 R 14 , --NR 13 R 14 , C 2 -C 6 alkoxyalkyl optionally substituted with --Si(CH 3 ) 3 ,, C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonylamino, --S(O) m R 13 , --SO 2 NR 13 R 14 , --NHSO 2 R 14 , --OCH 2 CO 2 R 13 , 2-(1-morpholino)ethoxy, or --C(R 14 )═N(OR 14 ); or a 5-or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur; or R 12 may be a 3-or 4-carbon chain attached to adjacent carbons on the ring to form a fused 5- or 6-membered ring, said 5- or 6-membered ring being optionally substituted on the aliphatic carbons with halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, or --NR 13 R 14 ; or, when R 12 is attached to a saturated carbon atom, it may be ═O or ═S; or when R 12 is attached to sulfur it may be ═O; R 12 , when a substituent on nitrogen, is selected from one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, --CH 2 NR 13 R 14 , --NR 13 R 14 , C 2 -C 6 alkoxyalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxycarbonyl, --CO 2 H, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, or --C(R 14 )═N(OR 14 ); R 12A , when a substituent on carbon, is selected from one or more of the following: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, C 7 -C 10 arylalkyl, C 1 -C 4 alkoxy, --CO 2 H, hydroxamic acid, hydrazide, boronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, --OR 13 , C 1 -C 4 alkyl substituted with --NH 2 , --NH 2 , --NHMe, C 2 -C 6 alkoxyalkyl optionally substituted with --Si(CH 3 ) 3 , C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --S(O) m Me, --SO 2 NH 2 , --NHSO 2 Me, --OCH 2 CO 2 R 13 , 2-(1-morpholino)ethoxy, 13 C(═NOH)NH 2 ; or a 5-or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur; or R 12A may be a 3-or 4-carbon chain attached to adjacent carbons on the ring to form a fused 5-or 6-membered ring, said 5-or 6-membered ring being optionally substituted on the aliphatic carbons with halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, or --NH 2 ; or, when R 12A is attached to a saturated carbon atom or sulfur, it may be ═O or ═S; R 12A , when a substituent on nitrogen, is selected from one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, --CH 2 NH 2 , --NH 2 , C 2 -C 6 alkoxyalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxycarbonyl, --CO 2 H, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, --C(═NOH)NH 2 ; R 13 is selected from: H; phenyl substituted with 0-3 R 11A ; benzyl substituted with 0-3 R 11A ; C 1 -C 6 alkyl substituted with 0-3 R 11A ; C 2 -C 4 alkenyl substituted with 0-3 R 11A ; C 1 -C 6 alkylcarbonyl substituted with 0-3 R 11A ; C 1 -C 6 alkoxycarbonyl substituted with 0-3 R 11A ; C 1 -C 6 alkylaminocarbonyl substituted with 0-3 R 11A ; C 3 -C 6 alkoxyalkyl substituted with 0-3 R 11A ; an amine protecting group when R 13 is bonded to N; or a hydroxy protecting group when R 13 is bonded to O; R 14 is hydrogen, hydroxy, CF 3 ; C 1 -C 6 alkyl substituted with 0-3 groups selected from OH, C 1 -C 4 alkoxy, halogen, NH 2 , C 1 -C 6 alkoxy; NH 2 ; --NH(C 1 -C 4 alkyl), C 2 -C 6 alkenyl; phenyl, benzyl, an amine protecting group when R 14 is bonded to N, or a hydroxy protecting group when R 14 is bonded to O; R 13 and R 14 can alternatively join to form --(CH 2 ) 4 --, --(CH 2 ) 5 --, --CH 2 CH 2 N(R 15 )CH 2 CH 2 --, or --CH 2 CH 2 OCH 2 CH 2 --; R 15 is H or CH 3 ; m is 0, 1 or 2; W is --N(R 22 )C(═Z)N(R 23 )--; wherein: Z is O; R 22 and R 23 are independently selected from the following: hydrogen; C 1 -C 8 alkyl substituted with 0-3 R 31 ; C 2 -C 8 alkenyl substituted with 0-3 R 31 ; C 2 -C 8 alkynyl substituted with 0-3 R 31 ; a C 3 -C 14 carbocyclic ring system substituted with 0-5 R 31 or R 32 ; a 5- to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-5 R 32 ; a5-to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-5 r 32 ) --OR 22a ; or --N(R 22a )(R 22b ); R 22a and R 22b are independently selected from the following: hydrogen; C 1 -C 8 alkyl substituted with 0-3 R 31 ; C 2 -C 8 alkenyl substituted with 0-3 R 31 ; C 2 -C 8 alkynyl substituted with 0-3 R 31 ; a C 3 -C 14 carbocyclic ring system substituted with 0-5 R 31 or R 32 ; a 5- to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-5 R 32 ; alternatively, R 22 can join with R 4 or R 4A to form a 5- or 6-membered fused heterocyclic ring or carbocyclic ring substituted with 0-2 R 12 , said heterocyclic ring containing 1-3 heteroatoms independently selected from N, S, or O; or alternatively, R 23 can join with R 7 or R 7A to form a 5- or 6-membered fused heterocyclic ring or carbocyclic ring substituted with 0-2 R 12 , said heterocyclic ring containing 1-3 heteroatoms independently selected from N, S, or O; or alternatively, R 22 can join with R 5 or R 6 to form a 0- to 7-membered bridge to form a carbocyclic or heterocyclic ring, said bridge being substituted with 0-2 R 12 and said bridge containing 0-3 heteroatoms independently selected from N, S, or O (i.e., a 0-membered bridge is formed when R 22 or R 23 are taken together with R 5 or R 6 to form a direct bond); or alternatively R23 can join with R7A to form a direct bond; or alternatively R22 can join with R4A to form a direct bond; R 31 is selected from one or more of the following: keto, halogen, cyano, --CH 2 NR 13 R 14 , --NR 13 R 14 , --CO 2 R 13 , --C(═O)R 11 , --OC(═O)R 13 , --OR 13 , C 2 -C 6 alkoxyalkyl, --S(O) m R 13 , --NHC(═NH)NHR 13 , --C(═NH)NHR 13 , --C(═O)NR 13 R 14 , --NR 14 C(═O)R 13 , ═NOR 14 , --NR 14 C(═O)OR 14 , --OC(═O)NR 13 R 14 , --NR 13 C(═O)NR 13 R 14 , --NR 13 C(═S)NR 13 R 14 , --NR 14 SO 2 NR 13 R 14 , --NR 14 SO 2 R 13 , --SO 2 NR 13 R 14 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 3 -C 10 cycloalkyl, C 3 -C 6 cycloalkylmethyl, benzyl, phenethyl, phenoxy, benzyloxy, nitro, C 7 -C 10 arylalkyl, hydroxamic acid, hydrazide, oxime, boronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, C 1 -C 4 alkyl substituted with --NR 13 R 14 , C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonylamino, --OCH 2 CO 2 R 13 , 2-(1-morpholino)ethoxy, azido, --C(R 14 )═N(OR 14 ); or - 3amino acids, linked together via amide bonds, said amino acid being linked via the amine or carboxylate terminus; a C 5 -C 14 carbocyclic residue substituted with 0-5 R 32 ; or a 5- to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-2 R 32 ; R 32 , when a substituent on carbon, is selected from one or more of the following: phenethyl, phenoxy, C 3 -C 10 cycloalkyl, C 3 -C 6 cycloalkylmethyl, C 7 -C 10 arylalkyl, hydrazide, oxime, boronic acid, C 2 -C 6 alkoxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 alkylcarbonyloxy, --NHSO 2 R 14 , benzyloxy, halogen, 2-(1-morpholino)ethoxy, --CO 2 R 13 , hydroxamic acid, --CONR 13 NR 13 R 14 , cyano, boronic acid, sulfonamide, --CHO, C 3 -C 6 cycloalkoxy, --NR 13 R 14 , --C(R 14 )═N(OR 14 ), NO 2 , --OR 13 , --N 40 R 41 , --SO m R 13 , --SO m NR 13 R 13 , --C(═O)NR 13 R 14 , --OC(═O)NR 13 R 14 , --C(═O)R 11 , --OC(═O)R 11 , --CO 2 R 13 , phenyl, --C(═O)NR 13 --(C 1 -C 4 alkyl)-NR 13 R 14 , --C(═O)NR 40 R 41 , C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 2 -C 4 haloalkenyl, C 1 -C 4 haloalkynyl, or --C(═O)NR 13 C(R 11 ) 2 NR 13 R 14 ; --C(═O)NR 13 C(R 11 ) 2 NR 13 NR 14 ; --C(═O)NR 13 C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O)NR 13 --(C 1 -C 4 alkyl)--NR 13 CO 2 R 13 ; --C(═O)N(R 13 )-(C 1 -C 4 alkyl)--R 11 ; or --C(═O)C(R 11 ) 2 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 NR 14 ; --C(═O)C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 R 14 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 CO 2 R 13 ; or C 1 -C 4 alkoxy substituted with 0-4 groups selected from: R 11 , C 3 -C 6 cycloalkyl, --CO 2 R 13 , --C(═O)NR 13 R 14 , --NR 13 R 14 or OH; C 1 -C 4 alkyl substituted with 0-4 groups selected from: R 11 , ═NR 14 , ═NNR 13 C(═O)NR 13 R 14 or --NR 13 R 14 , ═NNR 13 C(═O)OR 13 ,; C 2 -C 4 alkenyl substituted with 0-4 R 11 ; C 2 -C 4 alkynyl substituted with 0-4 R 11 ; a 5-or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, substituted with 0-2 R 12 ; or R 32 may be a 3-or 4-carbon chain attached to adjacent carbons on the ring to form a fused 5-or 6-membered ring, said 5-or 6-membered ring being optionally substituted on the aliphatic carbons with halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, or --NR 13 R 14 ; or, when R 32 is attached to a saturated carbon atom, it may be ═0 or ═S, ═NOH; or when R 32 is attached to sulfur it may be ═O; R 32 , when a substituent on nitrogen, is selected from one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, --CH 2 NR 13 R 14 , --NR 13 R 14 , C 2 -C 6 alkoxyalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxycarbonyl, --CO 2 H, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, or --C(R 14 )═N(OR 14 ); R 40 is selected from : H or C 1 -C 3 alkyl; R 41 is selected from: --C(═O)NR 13 R 14 ; --C(═O)NR 13 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O)H; --C(═O)R 11 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 R 14 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 CO 2 R 13 ; - 3amino acids linked together via amide bonds, and linked to the N atom via the carboxylate terminus; provided that: R 4 , R 4A , R 7 and R 7A are not all hydrogen; when R 4 , R 4A are hydrogen, R 22 is not hydrogen; and (b) a vehicle comprising a fatty acid ester of glycerol, a fatty acid ester of polyethylene glycol, or mixture thereof, wherein said vehicle has a hydrophil-lipophil balance of at least about 10.
2. A composition of claim 1 wherein said vehicle comprises a fatty acid ester of glycerol.
3. A composition of claim 2 wherein said fatty acid ester of glycerol is selected from one or more of the group consisting of mono-, di-, and triesters of glycerol or glycerol derivatives, wherein the fatty acid substituent is caprylate, caprate, laurate, myristate, palmitate, stearate, oleate, linoleate, linolenate, ricinoleate, arachidate, behenate, or hydroxylated products of these fatty acids.
4. A composition of claim 3 wherein said fatty acid ester of glycerol is selected from one or more of the group consisting of glycerol monoesters wherein the fatty acid substituent is caprate, laurate, oleate, or hydroxylated products of these fatty acids.
5. A composition of claim 1 wherein said vehicle comprises a fatty acid ester of polyethylene glycol.
6. A composition of claim 5 wherein said fatty acid ester of polyethylene glycol is selected from one or more of the group consisting of PEG stearate, PEG hydrogenated castor oil, PEG laurate, PEG apricot kernel oil esters, PEG caprylate, PEG caprate, PEG myristate, PEG palmitate, and PEG oleate.
7. A composition of claim 6 wherein said fatty acid ester of polyethylene glycol is selected from one or more of the group consisting of PEG-40 stearate, PEG-60 hydrogenated castor oil, PEG-32 laurate, PEG-40 hydrogenated castor oil, PEG-32 dilaurate, PEG-6 ethoxylated persic oil esters, PEG-8 caprylate, and PEG-8 caprate.
8. A composition of claim 1 wherein said vehicle comprises a mixture of a fatty acid ester of glycerol and a fatty acid ester of polyethylene glycol.
9. A composition of claim 8 wherein said mixture of fatty acid ester of glycerol and fatty acid ester of polyethylene glycol is a mixture having the characteristics set forth in Table A.
10. A composition of claim 8 wherein said mixture of fatty acid ester of glycerol and fatty acid ester of polyethylene glycol is a mixture having the characteristics set forth in Table B.
11. A composition of claim 1 wherein said hydrophil-lipophil balance is at least about 12.
12. A composition of claim 11 wherein said hydrophil-lipophil balance is between about 12 and about 18.
13. A composition of claim 12 wherein said hydrophil-lipophil balance is about 14.
14. A composition of claim 1 wherein said vehicle is a solid vehicle.
15. A composition of claim 1 wherein said vehicle is a liquid vehicle.
16. A composition of claim 1 wherein said Formula (I) compound is dispersed in said vehicle.
17. A composition of claim 16 wherein said dispersion is a homogeneous dispersion.
18. A composition of claim 1 wherein said Formula (I) compound is dissolved in said vehicle.
19. A composition of claim 1 wherein said composition is for oral administration.
20. A composition of claim 19 wherein said composition has an oral bioavailability of said compound of Formula (I) of at least about 30%.
21. A composition of claim 20 wherein said composition has an oral bioavailability of said compound of Formula (I) of at least about 50%.
22. A composition of claim 1 wherein said composition comprises between about 0.5% and about 50% of said compound of Formula (I) and between about 40% and about 95% of said fatty acid esters of glycerol, fatty acid esters of polyethylene glycol, or a mixture thereof.
23. A composition of claim 22 wherein said composition comprises between about 5% and about 20% of said compound of Formula (I) and between about 50% and about 90% of said fatty acid esters of glycerol, fatty acid esters of polyethylene glycol, or a mixture thereof.
24. A composition of claim 1 wherein said vehicle comprises additional vehicle components.
25. A composition of claim 24 wherein said additional vehicle components are selected from the group consisting of polyethylene glycol, propylene glycol, ethanol, or mixtures thereof.
26. A composition of claim 25 wherein said composition comprises between about 0.5% and about 50% of said compound of Formula (I) and between about 40% and about 95% of said fatty acid esters of glycerol, fatty acid esters of polyethylene glycol, or a mixture thereof, and between about 5% and about 50% of said additional vehicle components.
27. A composition of claim 26 wherein said composition comprises between about 0.5% and about 50% of said compound of Formula (I) and between about 40% and about 95% of said fatty acid esters of glycerol, fatty acid esters of polyethylene glycol, or a mixture thereof, and between about 10% and about 35% of said additional vehicle components.
28. A composition of claim 1 wherein, in said compound of Formula (I): R 4 and R 7 are independently selected from the following groups: hydrogen; C 1 -C 4 alkyl substituted with 0-3 R 11 ; C 3 -C 4 alkenyl substituted with 0-3 R 11 ; or C 3 -C 4 alkynyl substituted with 0-3 R 11 ; R 4A and R 7A are hydrogen; n is 1; R 5 is selected from fluoro or --OR 20 ; R 6 is independently selected from: hydrogen, fluoro or --OR 21 ; R 5 and R 6 can alternatively join to form an epoxide or aziridine ring; --OCH 2 SCH 2 O--; --OS(═O)O--; --OC(═O)O--; --OCH 2 O--; --OC(═S)O--; --OC(═O)C(═O)O--; --OC(CH 3 ) 2 O--; --OC(OCH 3 )(CH 2 CH 2 CH 3 )O--; or any group that, when administered to a mammalian subject, cleaves to form a free dihydroxyl; R 5a is selected from hydrogen or fluoro; R 6a is selected from: hydrogen or fluoro; R 5 and R 5a can alternatively join to form ═O, ═S, or a ketal ring; R 6 and R 6a can alternatively join to form ═O, ═S, or a ketal ring; R 20 and R 21 are independently selected from: hydrogen; C 1 -C 6 alkylcarbonyl; C 1 -C 6 alkoxycarbonyl; benzoyl; or any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl; R 11 is selected from one or more of the following: H, keto, halogen, cyano, --CH 2 NR 13 R 14 , --NR 13 R 14 , --CO 2 R 13 , --OC(═O)R 13 , --OR 13 , C 2 -C 4 alkoxyalkyl, --S(O) m R 13 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, or C 3 -C 10 cycloalkyl; a C 5 -C 14 saturated or partially unsaturated carbocyclic residue substituted with 0-3 R 12 ; aryl(C 1 -C 3 alkyl) substituted with 0-2 R 12 ; aryl substituted with 0-3 R 12 ; or a 5- to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-2 R 12 ; R 12 , when a substituent on carbon, is selected from one or more of the following: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, C 7 -C 10 arylalkyl, C 1 -C 4 alkoxy, 2-(1-morpholino)ethoxy, --CO 2 H, hydroxamic acid, hydrazide, --C(R 14 )═N(OR 14 ), cyano, oxime, boronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, --OR 13 , C 1 -C 4 alkyl substituted with --NR 13 R 14 , --NR 13 R 14 , C 2 -C 6 alkoxyalkyl, C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --S(O) m R 13 , --SO 2 NR 13 R 14 , or --NHSO 2 R 14 ; or a 5- or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur; or R 12 may be a 3- or 1-carbon chain attached to adjacent carbons on the ring to form a fused 5- or 6-membered ring, said 5- or 6-membered ring being optionally substituted on the aliphatic carbons with halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, or --NR 13 R 14 ; or, when R 12 is attached to a saturated carbon atom, it may be ═O or ═S; or when R 12 is attached to sulfur it may be ═O; R 12 , when a substituent on nitrogen, is selected from one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, --CH 2 NR 13 R 14 , --NR 13 R 14 , C 2 -C 6 alkoxyalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, or --CO 2 H; R 13 is H, C 1 -C 6 alkyl, C 3 -C 6 alkoxyalkyl, C 2 -C 4 alkenyl, phenyl, or benzyl; R 14 is OH, H, CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, NH 2 , C 2 -C 4 alkenyl, phenyl, or benzyl; R 13 and R 14 can alternatively join to form --(CH 2 ) 4 --, --(CH 2 ) 5 --, --CH 2 CH 2 N(R 15 )CH 2 CH 2 --, or --CH 2 CH 2 OCH 2 CH 2 --; R 15 is H or CH 3 ; m is 0, 1 or 2; W is --N(R 22 )C(═Z)N(R 23 )--; wherein: Z is O; R 22 and R 23 are independently selected from the following: hydrogen; C 1 -C 8 alkyl substituted with 0-3 R 31 ; C 3 -C 8 alkenyl substituted with 0-3 R 31 ; C 3 -C 8 alkynyl substituted with 0-3 R 31 ; or C 3 -C 6 cycloalkyl substituted with 0-3 R 31 ; R 31 is selected from one or more of the following: keto, halogen, cyano, --CH 2 NR 13 R 14 , --NR 13 R 14 , --CO 2 R 13 , --OC(═O)R 13 , --OR 13 , C 2 -C 4 alkoxyalkyl, --S(O) m R 13 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 3 -C 10 cycloalkyl, benzyl, phenethyl, phenoxy, benzyloxy, nitro, C 7 -C 10 arylalkyl, hydroxamic acid, hydrazide, oxime, boronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, C 1 -C 4 alkyl substituted with --NR 13 R 14 , C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --OCH 2 CO 2 H, 2-(1-morpholino)ethoxy, or --C(R 14 )═N(OR 14 ); or a C 5 -C 14 saturated or partially unsaturated carbocyclic residue substituted with 0-3 R 32 ; aryl substituted with 0-3 R 32 ; or a 5- to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-2 R 32 ; R 32 , when a substituent on carbon, is selected from one or more of the following: phenethyl, phenoxy, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, C 7 -C 10 arylalkyl, hydrazide, oxime, boronic acid, C 2 -C 6 alkoxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 alkylcarbonyloxy, --NHSO 2 R 14 , benzyloxy, halogen, 2-(1-morpholino)ethoxy, --CO 2 R 13 , hydroxamic acid, --CONR 13 NR 13 R 14 , cyano, boronic acid, sulfonamide, --CHO, C 3 -C 6 cycloalkoxy, --NR 13 R 14 , --C(R 14 )═N(OR 14 ), NO 2 , --OR 13 , --NR 40 R 41 , --SO m R 13 , --SO m NR 13 R 14 , --C(═O)NR 13 R 14 , --OC(═O)NR 13 R 14 , --C(═O)R 11 , --OC(═O)R 11 , --OCO 2 R 13 , phenyl, --C(═O)NR 13 -(C 1 -C 4 alkyl)-NR 13 R 14 , --C(═O)NR 40 R 41 , C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 2 -C 4 haloalkenyl, C 1 -C 4 haloalkynyl, or --(═O)NR 13 C(R 11 ) 2 NR 13 R 14 ; --C(═O)NR 13 C(R 11 ) 2 NR 13 NR 14 ; --C(═O)NR 13 C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O)NR 13 -(C 1 -C 4 alkyl)--NR 13 CO 2 R 13 ; or --C(═O)C(R 11 ) 2 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 NR 14 ; --C(═O)C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O) -(C 1 -C 4 alkyl)--NR 13 R 14 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 CO 2 R 13 ; or C 1 -C 4 alkoxy substituted with 0-3 groups selected from: R 11 , C 3 -C 6 cycloalkyl, --CO 2 R 13 , --C(═O)NR 13 R 14 , --NR 13 R 14 or OH; C 1 -C 4 alkyl substituted with 0-3 groups selected from: R 11 , ═NR 14 , ═NNR 13 C(═O)NR 13 R 14 or --NR 13 R 14 ; C 2 -C 4 alkenyl substituted with 0-3 R 11 ; C 2 -C 4 alkynyl substituted with 0-3 R 11 ; a 5- or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, substituted with 0-2 R 12 ; or R 32 may be a 3-or 4-carbon chain attached to adjacent carbons on the ring to form a fused 5- or 6-membered ring, said 5-or 6-membered ring being optionally substituted on the aliphatic carbons with halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, or --NR 13 R 14 ; or, when R 32 is attached to a saturated carbon atom, it may be ═O or ═S; or when R 12 is attached to sulfur it may be ═O; R 32 , when a substituent on nitrogen, is selected from one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, --CH 2 NR 13 R 14 , --NR 13 R 14 , C 2 -C 6 alkoxyalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, --CO 2 H, or --C(R 14 )═N(OR 14 ); R 40 is selected from: H, C 1 -C 3 alkyl; R 41 is selected from: --C(═O)NR 13 R 14 ; --C(═O)NR 13 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O)H; --C(═O)R 11 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 R 14 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 CO 2 R 13 ; or - 3amino acids linked together via amide bonds, and linked to the N atom via the carboxylate terminus; provided that: R 4 , R 4A , R 7 , and R 7A are not all hydrogen; and when R 4 and R 4A are hydrogen, R 22 is not hydrogen.
29. A composition of claim 1 wherein said compound of Formula (I) is a compound of formula: ##STR17## or a pharmaceutically acceptable salt thereof, wherein: R 4 and R 7 are independently selected from the following groups: hydrogen; C 1 -C 3 alkyl substituted with 0-1 R 11 ; R 5 is --OR 20 ; R 6 is hydrogen or --OR 21 ; R 20 and R 21 are independently hydrogen or any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl; R 11 is selected from one or more of the following: H; halogen; --OR 13 ; C 3 -C 10 cycloalkyl substituted with 0-2 R 12 ; C 1 -C 4 alkyl substituted with 0-2 R 12 ; aryl(C 1 -C 3 alkyl) substituted with 0-2 R 12 ; aryl substituted with 0-2 R 12 ; or a heterocyclic ring system selected from pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, indolyl, quinolinyl, isoquinolinyl, oxazolidinyl, said heterocyclic ring system being substituted with 0-2 R 12 ; R 12 , when a substituent on carbon, is selected from one or more of the following: benzyloxy, halogen, methyl, C 1 -C 4 alkoxy, CF 3 , 2-(1-morpholino)ethoxy, --CO 2 H, hydroxamic acid, hydrazide, --(R 14 )═N(OR 14 ), cyano, boronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, C 1 -C 4 alkyl substituted with --NR 13 R 14 , --NR 13 R 14 , hydroxy, hydroxymethyl; or R 12 , when a substituent on nitrogen, is methyl; R 13 is H, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, or benzyl; R 14 is OH, H, CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, NH 2 , C 2 -C 4 alkenyl, or benzyl; R 13 and R 14 can alternatively join to form --(CH 2 ) 4 --, --(CH 2 ) 5 --, --CH 2 CH 2 N(R 15 )CH 2 CH 2 --, or --CH 2 CH 2 OCH 2 CH 2 --; R 15 is H or CH 3 ; W is selected from: --N(R 22 )C(═Z)N(R 23 )--; Z is O, R 22 and R 23 are independently selected from the following: hydrogen; C 1 -C 8 alkyl substituted with 0-3 R 31 ; C 2 -C 6 alkenyl substituted with 0-3 R 31 ; or C 2 -C 4 alkynyl substituted with 0-3 R 31 ; R 31 is selected from one or more of the following: halogen, --OR 13 , C 1 -C 4 alkyl, C 3 -C 10 cycloalkyl, --(R 14 )═N(OR 14 ), --CO 2 R 13 , --S(O) m R 13 ; aryl substituted with 0-5 R 32 ; or a heterocyclic ring system chosen from pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, indolyl, quinolinyl, isoquinolinyl, oxazolidinyl, said heterocyclic ring being substituted with 0-2 R 32 ; R 32 , when a substituent on carbon, is selected from one or more of the following: benzyloxy, halogen, 2-(1-morpholino)ethoxy, --CO 2 R 13 , hydroxamic acid, --CONR 13 NR 13 R 14 , cyano, boronic acid, sulfonamide, --CHO, C 3 -C 6 cycloalkoxy, --NR 13 R 14 , --C(R 14 )═N(OR 14 ), NO 2 , --OR 13 , --NR 40 R 41 , --SO m R 13 , --SO m NR 13 R 14 , --C(═O)NR 13 R 14 , --OC(═O)NR 13 R 14 , --C(═O)R 11 , --OC(═O) R 11 , --OCO 2 R 13 , phenyl, --C(═O)NR 13 --(C 1 -C 4 alkyl)--NR 13 R 14 , --C(═O)N 40 R 41 , C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 2 -C 4 haloalkenyl, C 1 -C 4 haloalkynyl, --C(═O)NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 NR 14 ; --C(═O)C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O)--(C 1 -C 4 alkyl)--NR 13 R 14 ; --C(═O)-(C 1 -C 4 alkyl)-NR 13 CO 2 R 13 ; or C 1 -C 4 alkoxy substituted with 0-3 groups selected from: R 11 , C 3 -C 6 cycloalkyl, --C(═O)NR 13 R 14 , --NR 13 R 14 or OH; C 1 -C 4 alkyl substituted with 0-3 groups selected from: R 11 , ═NR 14 , ═NNR 13 C(═O)NR 13 R 14 or --NR 13 R 14 ; C 2 -C 4 alkenyl substituted with 0-3 R 11 ; C 2 -C 4 alkynyl substituted with 0-3 R 11 ; a 5- or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur; R 32 , when a substituent on nitrogen, is methyl; m is 0, 1, or 2; R 40 is selected from: H, or C 1 -C 3 alkyl; R 41 is selected from: --C(═O)NR 13 R 14 ; --C(═O)NR 13 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O)H; --C(═O)R 11 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 R 14 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 CO 2 R 13 ; - 3amino acids linked together via amide bonds, and linked to the N atom via the carboxylate terminus; provided that: R 4 and R 7 are not both hydrogen; when W is --C(═Z)--, R 4 and R 7 are not hydrogen; and when R 4 is hydrogen, is not hydrogen R 22 .
30. A composition of claim 29 wherein, in said compound of Formula (I): R 4 and R 7 are selected from benzyl, fluorobenzyl, pyrrolylmethyl, methoxybenzyl, isobutyl, nitrobenzyl aminobenzyl, thienylmethyl, or hydroxybenzyl; R 5 is --OH; R 6 is hydrogen or --OH; R 13 is H, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, or benzyl; R 14 is OH, H, CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, NH 2 , C 2 -C 4 alkenyl, or benzyl; R 13 and R 14 can alternatively join to form --(CH 2 ) 4 --, --(CH 2 ) 5 --, --CH 2 CH 2 N(R 15 )CH 2 CH 2 --, or --CH 2 CH 2 OCH 2 CH 2 --; W is selected from: R 22 and R 23 are independently selected from the following: hydrogen; C 1 -C 8 alkyl substituted with 0-2 R 31 ; C2-C 6 alkenyl substituted with 0-2 R 31 ; or C 2 -C 4 alkynyl substituted with 0-2 R 31 ; R 31 is selected from one or more of the following: halogen, --OR 13 , C 1 -C 4 alkyl, C 3 -C 10 cycloalkyl, --(R 14 )═N(OR 14 ), --CO 2 R 13 , --S(O) m R 13 ; aryl substituted with 0-5 R 32 ; or a heterocyclic ring system chosen from pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, indolyl, quinolinyl, isoquinolinyl, oxazolidinyl, benzimidazolyl, benzotriazolyl, indazolyl, benzoxazolinyl, benzoxazolyl, said heterocyclic ring being substituted with 0-2 R 32 ; R 32 , when a substituent on carbon, is selected from one or more of the following: --CONH 2 , --CO 2 H, --CHO, --CH 2 NHOH, --CH 2 NR 13 R 14 , --NR 13 R 14 , hydroxy, hydroxymethyl, --C(R 14 )═N(OR 14 ), halogen, methoxy, methyl, nitro, cyano, allyloxy, --CO 2 CH 3 , --NHCHO, --NHCOCH 3 , --OCO 2 CH 3 , --CH═NCH 2 CH 2 OH, --OCONHCH 2 C 6 H 5 , --OCONHCH 3 , oxazolidinyl, --C═CH 2 OH, --COCH 3 , hydroxyethyl, C 1 -C 3 alkyl (said alkyl substituted with 0-4 halogen, or OH), tetrazolyl, --OCH 2 CONH 2 , --CONHNH 2 , --CH═NNHCONH 2 , --CONHOCH 3 , --CH 2 CH(OH)CH 2 OH, adamantamido, hydroxyethoxy, dihydroxyethyl, --C(NH 2 )═NH, --CONHCH 3 , --B(OH) 2 , benzyloxy, --CONHCH 2 CH 3 , --CON(CH 2 CH 3 ) 2 , methylthio, --SO 2 CH 3 , --NHCONH 2 , --NHCONHCH 3 , --NHCOCH 2 N(CH 3 ) 2 , --NHCOCH 2 NHCH 3 , --NHCOCH 2 NHCO 2 CH 2 C 6 H 5 , --NHCOCH 2 NH 2 , --NHCOCH(CH 3 )NHCO 2 CH 2 C 6 H 5 , --NHCOCH(CH 2 C 6 H 5 )NHCO 2 CH 2 C 6 H 5 , --NHCOCH(CH 3 )NH 2 , --NHCOCH(CH 2 C 6 H5)NH 2 , --CO 2 CH 2 CH 3 , --CONHCH 2 CH 2 CH 3 , --CONHCH(CH 3 ) 2 , --CH 2 -imidazole, --COC(CH 3 ) 3 , --CH(OH)CF 3 , --CO-imidazole, --CO-pyrazolyl, oxadiazolidinonyl, --COCF 3 , --COCH 2 CH 3 , --COCH 2 CH 2 CH 3 , pyrazolyl, --SO 2 NH 2 , --C(CH 2 CH 3 )═N(OH) or --C(CF 3 )═N(OH), phenyl, acetoxy, hydroxyamino, --N(CH 3 )(CHO), cyclopropylmethoxy, --CONR 13 R 14 , --CONHOH, (diethylaminoethyl)aminocarbonyl, (N-ethyl, N-methylaminoethyl )aminocarbonyl, (4-methylpiperazinylethyl)aminocarbonyl, pyrrolidinylethyl)aminocarbonyl, (piperidinylethyl)aminocarbonyl, --NHCOCH 2 NHCH 3 , N-(2-(4-morpholino)ethyl)aminocarbonyl, or N-(2-(N,N-dimethylamino)ethyl)aminocarbonyl; and R 32 when a substituent on nitrogen, is methyl.
31. A composition of claim 1 wherein said compound of Formula (I) is a compound of the formula: ##STR18## wherein: Z is O. R 4 and R 7 are independently selected from: benzyl, fluorobenzyl, pyrrolylmethyl, methoxybenzyl, isobutyl, nitrobenzyl aminobenzyl, thienylmethyl, or hydroxybenzyl; R 22 and R 23 are independently selected from the group consisting of: hydrogen, allyl, methyl, ethyl, propyl, cyclopropylmethyl, n-butyl, i-butyl, CH 2 CH═C(CH 3 ) 2 , pyridinylmethyl, methallyl, n-pentyl, i-pentyl, hexyl, benzyl, isoprenyl, propargyl, picolinyl, methoxyethyl, cyclohexylmethyl, dimethyl-butyl, ethoxyethyl, methyl-oxazolinylmethyl, naphthylmethyl, methyloxazolinylmethyl, vinyloxyethyl, pentafluorobenzyl, quinolinylmethyl, carboxybenzyl, chloro-thienyl, benzyloxybenzyl, phenylbenzyl, adamantylethyl, cyclopropylmethoxybenzyl, methoxybenzyl, methylbenzyl, ethoxybenzyl, hydroxybenzyl, hydroxymethylbenzyl, aminobenzyl, formylbenzyl, cyanobenzyl, cinnamyl, allyloxybenzyl, fluorobenzyl, difluorobenzyl, chlorobenzyl, chloromethylbenzyl, fluoromethylbenzyl, iodobenzyl, bromobenzyl, cyclobutylmethyl, formaldoximebenzyl, cyclopentylmethyl, nitrobenzyl, (H 2 NC (═O))-benzyl, carbomethoxybenzyl, carboethoxybenzyl, tetrazolylbenzyl, and dimethylallyl, aminomethylbenzyl, (O-benzyl-formaldoxime)benzyl, (O-methyl-formaldoxime)benzyl, (CH 3 O 2 CO)-benzyl, (HOCH 2 CH 2 N═CH)-benzyl, N-benzylaminocarbonylbenzyl, N-methylaminobenzyl, N-ethylaminobenzyl, N-ethylaminomethylbenzyl, acetylbenzyl, acetoxybenzyl, N-hydroxylaminobenzyl, phenylmethylboronic acid, N-hydroxylaminomethylbenzyl, (hydroxyl)ethylbenzyl, (CH 3 C(═NOH))-benzyl, (H 2 NNHC(═O))-benzyl, (H 2 NC (═O)NHN═CH)-benzyl, (CH 3 ONHC(═O))-benzyl, (HONHC(═O))-benzyl, (CH 3 NHC(═O))-benzyl, N,N-dimethylaminocarbonylbenzyl, (HOCH 2 CH(OH)CH 2 O)-benzyl, hydroxyethoxybenzyl (oxazolidinyl)-benzyl, (hydroxyl)hexyl, hexenyl, (hydroxy)octyl, (hydroxyl)pentyl, (carboxy)pentyl, (carbomethoxy)pentyl, (methylthio)benzyl, (methylsulfonyl)benzyl, N,N-dimethylaminomethylbenzyl, N-methylaminomethylbenzyl, glycylaminobenzyl, N,N-dimethylglycylaminobenzyl, alanylaminobenzyl, (N-phenylmethoxycarbonyl)alanylaminobenzyl, phenylalanylaminobenzyl, (N-phenylmethoxycarbonyl) phenylalanylaminobenzyl, (CH 3 CH 2 NHC(═O))-benzyl, N,N-diethylaminocarbonylbenzyl, N-ethylaminocarbonylbenzyl, N-propylaminocarbonylbenzyl, N,N-diisopropylaminocarbonylbenzyl, N,N-di-n-propylaminocarbonylbenzyl, (hydroxypropynyl)benzyl, (imidazolyl-C(═O))-benzyl, (pyrazolyl-C(═O))-benzyl, (pyridylmethylaminocarbonyl)benzyl, (oxadiazolidinonyl)benzyl, trifluoroacetylbenzyl, (pyrazolyl) benzyl, (H 2 NSO 2 )-benzyl, dihydroxyethylbenzyl, (MeHNC(═O)NH)-benzyl, (H 2 NC(═O)NH)-benzyl, (HC(═O)NH)-benzyl, methanesulfonylpentyl, methoxypentyl, N-formyl-N-methylaminobenzyl, acetylaminobenzyl, propionylbenzyl, butyrylbenzyl, (CH 3 CH 2 C(═NOH))-benzyl, (trifluorohydroxyethyl)benzyl, (CF 3 C(═NOH))-benzyl, (N-methylglycyl)aminobenzyl, ((4-morpholino) ethyl)aminocarbonylbenzyl, (N,N-dimethylaminoethyl)aminocarbonylbenzyl, (N,N-diethylaminoethyl)aminocarbonylbenzyl, (4-methylpiperazin-1-ylethyl)aminocarbonylbenzyl, (benzyl-NHC(═O)O)benzyl, (CH 3 NHC(═O)O)benzyl, (NH 2 C(═O)CH 2 O)benzyl, (NH 2 C(═NH))benzyl, ((N-phenylmethoxycarbonyl)glycylamino)benzyl, (imidazolylmethyl)benzyl, ((CH 3 ) 3 C-C(═O))benzyl, (N-methyl-N-ethylaminoethyl)aminocarbonylbenzyl, (pyrrolidinylethyl)aminocarbonylbenzyl, or (piperidinylethyl)aminocarbonylbenzyl, (H 2 NC(═NOH))benzyl, (H 2 NC(═NOH))fluorobenzyl, benzimidazolylmethyl, benzotriazolylmethyl, indazolylmethyl, benzoxazolinylmethyl, benzisoxazolylmethyl, thienylmethyl, furylmethyl.
32. A composition of claim 1 wherein said compound of Formula (I) is a compound of the formula: ##STR19## wherein R 22 and R 23 are independently selected from the group consisting of: hydrogen, allyl, methyl, ethyl, propyl, cyclopropylmethyl, n-butyl, i-butyl, CH 2 CH═C(CH 3 ) 2 , pyridinylmethyl, methallyl, n-pentyl, i-pentyl, hexyl, benzyl, isoprenyl, propargyl, picolinyl, methoxyethyl, cyclohexylmethyl, dimethyl-butyl, ethoxyethyl, methyl-oxazolinylmethyl, naphthylmethyl, methyloxazolinylmethyl, vinyloxyethyl, pentafluorobenzyl, quinolinylmethyl, carboxybenzyl, chloro-thienyl, benzyloxybenzyl, phenylbenzyl, adamantylethyl, cyclopropylmethoxybenzyl, methoxybenzyl, methylbenzyl, ethoxybenzyl, hydroxybenzyl, hydroxymethylbenzyl, aminobenzyl, formylbenzyl, cyanobenzyl, cinnamyl, allyloxybenzyl, fluorobenzyl, difluorobenzyl, chlorobenzyl, chloromethylbenzyl, fluoromethylbenzyl, iodobenzyl, bromobenzyl, cyclobutylmethyl, formaldoximebenzyl, cyclopentylmethyl, nitrobenzyl, (H 2 NC(═O))-benzyl, carbomethoxybenzyl, carboethoxybenzyl, tetrazolylbenzyl, and dimethylallyl, aminomethylbenzyl, (O-benzyl-formaldoxime)benzyl, (O-methyl-formaldoxime)benzyl, (CH 3 O 2 CO)-benzyl, (HOCH 2 CH 2 N═CH)-benzyl, N-benzylaminocarbonylbenzyl, N-methylaminobenzyl, N-ethylaminobenzyl, N-ethylaminomethylbenzyl, acetylbenzyl, acetoxybenzyl, N-hydroxylaminobenzyl, phenylmethylboronic acid, N-hydroxylaminomethylbenzyl, (hydroxyl) ethylbenzyl, (CH 3 C(═NOH))-benzyl, (H 2 NNHC (═O))-benzyl, (H 2 NC(═O) NHN═CH)-benzyl, (CH 3 ONHC(═O))-benzyl, (HONHC(═O))-benzyl, (CH 3 NHC(═O))-benzyl, N,N-dimethylaminocarbonylbenzyl, (HOCH 2 CH(OH)CH 2 O)-benzyl, hydroxyethoxybenzyl (oxazolidinyl)-benzyl, (hydroxyl)hexyl, hexenyl, (hydroxy)octyl, (hydroxyl)pentyl, (carboxy)pentyl, (carbomethoxy)pentyl, (methylthio)benzyl, (methylsulfonyl)benzyl, N,N-dimethylaminomethylbenzyl, N-methylaminomethylbenzyl, glycylaminobenzyl, N,N-dimethylglycylaminobenzyl, alanylaminobenzyl, (N-phenylmethoxycarbonyl)alanylaminobenzyl, phenylalanylaminobenzyl, (N-phenylmethoxycarbonyl) phenylalanylaminobenzyl, (CH 3 CH 2 NHC(═O))-benzyl, N,N-diethylaminocarbonylbenzyl, N-ethylaminocarbonylbenzyl, N-propylaminocarbonylbenzyl, N,N-diisopropylaminocarbonylbenzyl, N, N-di-n-propylaminocarbonylbenzyl, (hydroxypropynyl)benzyl, (imidazolyl-C(═O))-benzyl, (pyrazolyl-C(═O))-benzyl, (pyridylmethylaminocarbonyl)benzyl, (oxadiazolidinonyl)benzyl, trifluoroacetylbenzyl, (pyrazolyl)benzyl, (H 2 NSO 2 )-benzyl, dihydroxyethylbenzyl, (MeHNC (═O)NH)-benzyl, (H 2 NC(═O)NH)-benzyl, (HC(═O)NH)-benzyl, methanesulfonylpentyl, methoxypentyl, N-formyl-N-methylaminobenzyl, acetylaminobenzyl, propionylbenzyl, butyrylbenzyl, (CH 3 CH 2 C(═NOH))-benzyl, (trifluorohydroxyethyl)benzyl, (CF 3 C(═NOH))-benzyl, (N-methylglycyl)aminobenzyl, ((4-morpholino)ethyl)aminocarbonylbenzyl, (N,N-dimethylaminoethyl)aminocarbonylbenzyl, (N,N-diethylaminoethyl)aminocarbonylbenzyl, (4-methylpiperazin-1-ylethyl)aminocarbonylbenzyl, (benzyl-NHC(═O)O)benzyl, (CH 3 NHC(═O)O)benzyl, (NH 2 C(═O)CH 2 O)benzyl, (NH 2 C(═NH))benzyl, ((N-phenylmethoxycarbonyl)glycylamino )benzyl, (imidazolylmethyl)benzyl, ((CH 3 ) 3 C-C(═O))benzyl, (N-methyl-N-ethylaminoethyl)aminocarbonylbenzyl, (pyrrolidinylethyl)aminocarbonylbenzyl, or (piperidinylethyl)aminocarbonylbenzyl, (H 2 NC(═NOH))benzyl, (H 2 NC(═NOH))fluorobenzyl, benzimidazolylmethyl, benzotriazolylmethyl, indazolylmethyl, benzoxazolinylmethyl, benzisoxazolylmethyl, thienylmethyl, furylmethyl.
33. A composition of claim 1 wherein said compound of Formula (I) is a compound of the formula: ##STR20## selected from the group consisting of: the compound wherein R 22 is allyl and R 23 is allyl; the compound wherein R 22 is propyl and R 23 is propyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is cyclopropylmethyl; the compound wherein R 22 is n-hexyl and R 23 is n-hexyl; the compound wherein R 22 is n-butyl and R 23 is n-butyl; the compound wherein R 22 is CH 2 CH═C(CH 3 ) 2 and R 23 is CH 2 CH═C(CH 3 ) 2 ; the compound wherein R 22 is CH 2 CH═C(CH 3 ) 2 and R 23 is H; the compound wherein R 22 is i-pentyl and R 23 is i-pentyl; the compound wherein R 22 is 2-methallyl and R 23 is 2-methallyl; the compound wherein R 22 is n-pentyl and R 23 is n-pentyl; the compound wherein R 22 is benzyl and R 23 is benzyl; the compound wherein R 22 is i-hexyl and R 23 is i-hexyl; the compound wherein R 22 is allyl and R 23 is isoprenyl; the compound wherein R 22 is 1-cinnamyl and R 23 is 1-cinnamyl; the compound wherein R 22 is 4-fluorobenzyl and R 23 is 4-fluorobenzyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is benzyl; the compound wherein R 22 is allyl and R 23 is benzyl; the compound wherein R 22 is CH 2 CH═C(CH 3 ) 2 and R 23 is cyclopropylmethyl; the compound wherein R 22 is 2-naphthylmethyl and R 23 is 2-napthylmethyl; the compound wherein R 22 is n-butyl and R 23 is benzyl; the compound wherein R 22 is allyl and R 23 is cyclopropylmethyl; the compound wherein R 22 is n-butyl and R 23 is cyclopropylmethyl; the compound wherein R 22 is CH 2 CH═C(CH 3 ) 2 and R 23 is benzyl; the compound wherein R 22 is benzyl and R 23 is ethyl; the compound wherein R 22 is benzyl and R 23 is 4-pyridinylmethyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is 4-pyridinylmethyl; the compound wherein R 22 is benzyl and R 23 is cyclopentylmethyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is cyclopentylmethyl; the compound whereran R 22 is benzyl and R 23 is n-propyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is cinnamyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is 2-naphthylmethyl; the compound wherein R 22 is cyclopentylmethyl and R 23 is 2-naphthylmethyl; the compound wherein R 22 is benzyl and R 23 is 2-naphthylmethyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is 2-pyridinylmethyl; the compound wherein R 22 is 3-cyanobenzyl and R 23 is 3-cyanobenzyl; the compound wherein R 22 is allyl and R 23 is 2-naphthylmethyl; the compound wherein R 22 is n-propyl and R 23 is 2-naphthylmethyl; the compound wherein R 22 is n-butyl and R 23 is 2-naphthylmethyl; the compound wherein R 22 is hydrogen and R 23 is 2-naphthylmethyl; the compound wherein R 22 is 4-pyridinylmethyl and R 23 is 2-naphthylmethyl; the compound wherein R 22 is allyl and R 23 is cyclopentylmethyl; the compound wherein R 22 is allyl and R 23 is 2-quinolinylmethyl; the compound wherein R 22 is 3-pyridinylmethyl and R 23 is cyclopropylmethyl; the compound wherein R 22 is 3-pyridinylmethyl and R 23 is 2-naphthylmethyl; the compound wherein R 22 is 3-hydroxybenzyl and R 23 is 3-hydroxybenzyl; the compound wherein R 22 is vinylbenzyl and R 23 is vinylbenzyl; the compound wherein R 22 is 3-allyloxybenzyl and R 23 is 3-hydroxybenzyl; the compound wherein R 22 is 3-pyridinylmethyl and R 23 is 3-pyridinylmethyl; the compound wherein R 22 is 2-naphthylmethyl and R 23 is 4-fluorobenzyl; the compound wherein R 22 is 4-hydroxybenzyl and R 23 is 4-hydroxybenzyl; the compound wherein R 22 is 3-hydroxymethylbenzyl and R 23 is 3-hydroxymethylbenzyl; the compound wherein R 22 is 3-carbomethoxybenzyl and R 23 is 3-carbomethoxybenzyl; the compound wherein R 22 is 4-hydroxymethylbenzyl and R 23 is 4-hydroxymethylbenzyl; the compound wherein R 22 is 3-formylbenzyl and R 23 is 3-formylbenzyl; the compound wherein R 22 is 4-cyanobenzyl and R 23 is 4-cyanobenzyl; the compound wherein R 22 is 4-formylbenzyl and R 23 is 4-formylbenzyl; the compound wherein R 22 is 4-hydroxybenzyl and R 23 is 2-propyl; the compound wherein R 22 is 3-hydroxybenzyl and R 23 is 2-propyl; the compound wherein R 22 is 3-carboxybenzyl and R 23 is 3-carboxybenzyl; the compound wherein R 22 is 3-formaldoximebenzyl and R 23 is 3-formaldoximebenzyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is 3-hydroxybenzyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is 4-hydroxybenzyl; the compound wherein R 22 is cyclobutylmethyl and R 23 is cyclobutylmethyl; the compound wherein R 22 is cyclopentylmethyl and R 23 is cyclopentylmethyl; the compound wherein R 22 is 3n-butyl and R 23 is CH 2 CH═C(CH 3 ) 2 ; the compound wherein R 22 is n-butyl and R 23 is cyclopentylmethyl; the compound wherein R 22 is benzyl and R 23 is H; the compound wherein R 22 is 3-fluorobenzyl and R 23 is 3-fluorobenzyl; the compound wherein R 22 is 3-methoxybenzyl and R 23 is 3-methoxybenzyl; the compound wherein R 22 is 3,4-difluorobenzyl and R 23 is 3,4-difluorobenzyl; the compound wherein R 22 is 4-methylbenzyl and R 23 is 4-methylbenzyl; the compound wherein R 22 is 4-chlorobenzyl and R 23 is 4-chlorobenzyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is 4-fluorobenzyl; the compound wherein R 22 is 3-chlorobenzyl and R 23 is 3-chlorobenzyl; the compound wherein R 22 is 3-nitrobenzyl and R 23 is 3-nitrobenzyl; the compound wherein R 22 is 3-methylbenzyl and R 23 is 3-methylbenzyl; the compound wherein R 22 is 3-bromobenzyl and R 23 is 3-bromobenzyl; the compound wherein R 22 is 4-fluorobenzyl and R 23 is H; the compound wherein R 22 is cyclopropylmethyl and R 23 is 3-chlorobenzyl; the compound wherein R 22 is 3-aminobenzyl and R 23 is 3-aminobenzyl; the compound wherein R 22 is 4-aminobenzyl and R 23 is 4-aminobenzyl; the compound wherein R 22 is 3-nitrobenzyl and R 23 is H; the compound wherein R 22 is 3-(NHCHO)benzyl and R 23 is 3-(NHCHO)benzyl; the compound wherein R 22 is 3-(NHCOCH 3 )benzyl and R 23 is 3-(NHCOCH 3 )benzyl; the compound wherein R 22 is 3,4-dihydroxybenzyl and R 23 is 3,4-dihydroxybenzyl; the compound wherein R 22 is 3-formaldoximebenzyl and R 23 is 3-(N-hydroxy)aminomethylbenzyl; the compound wherein R 22 is 3-(N-hydroxy)aminomethylbenzyl and R 23 is 3-(N-hydroxy)aminomethylbenzyl; the compound wherein R 22 is 3-(CH 3 OC(═O)O--)benzyl and R 23 is 3-(CH 3 OC(═O)O--)benzyl; the compound wherein R 22 is 3-(1-hydroxyethyl)benzyl and R 23 is 3-(1-hydroxyethyl)benzyl; the compound wherein R 22 is 3-(HOCH 2 CH 2 N═CH)benzyl and R 23 is 3-(HOCH 2 CH 2 N═CH)benzyl; the compound wherein R 22 is 3-(HOCH 2 CH 2 N═CH)benzyl and R 23 is 3-(2-oxazolidinyl)benzyl; the compound wherein R 22 is 3-(C 6 H 5 CH 2 NHC(═O)O)benzyl and R 23 is 3-(C 6 HSCH 2 NHC(═O)O) benzyl; the compound wherein R 22 is 3-(CH 3 NHC(═O)O)benzyl and R 23 is 3-(CH 3 NHC(═O)O)benzyl; the compound wherein R 22 is 3-(HOCH 2 CC)benzyl and R 23 is 3-bromobenzyl; the compound wherein R 22 is 3-acetylbenzyl and R 23 is 3-bromobenzyl; the compound wherein R 22 is 3-acetylbenzyl and R 23 is 3-acetylbenzyl; the compound wherein R 22 is 3-(CH 3 C(═NOH))benzyl and R 23 is 3-(CH 3 C(═NOH))benzyl; the compound wherein R 22 is 3-(1-hydroxyethyl)benzyl and R 23 is 3-bromobenzyl; the compound wherein R 22 is 3-(chloromethyl)benzyl and R 23 is 3-(chloromethyl)benzyl; the compound wherein R 22 is 3-(5-tetrazolyl)benzyl and R 23 is cyclopropylmethyl; the compound wherein R 22 is 3-cyanobenzyl and R 23 is 3-formylbenzyl; the compound wherein R 22 is 4-acetoxybenzyl and R 23 is 4-hydroxybenzyl; the compound wherein R 22 is 3-aminocarbonylbenzyl and R 23 is 3-aminocarbonylbenzyl; the compound wherein R 22 is 3-(H 2 NCOCH 2 O)benzyl and R 23 is 3-(H 2 NCOCH 2 O)benzyl; the compound wherein R 22 is 3-hydroxybenzyl and R 23 is H; the compound wherein R 22 is 3-methylbenzyl and R 23 is 3-hydroxybenzyl; the compound wherein R 22 is 2-naphthylmethyl and R 23 is 3-hydroxybenzyl; the compound wherein R 22 is 3-(H 2 NNHC(═O))-benzyl and R 23 is 3-(H 2 NNHC(═O))-benzyl; the compound wherein R 22 is 4-(H 2 NNHC(═O))-benzyl and R 23 is 4-(H 2 NNHC(═O))-benzyl; the compound wherein R 22 is 4-hydroxymethylbenzyl and R 23 is 3-hydroxybenzyl; the compound wherein R 22 is 3-(H 2 NC(═O)NHN═CH)-benzyl and R 23 is 3-(H 2 NC(═O)NHN═CH)-benzyl; the compound wherein R 22 is 3-[(N-methoxy)aminocarbonyl]-benzyl and R 23 is 3-[(N-methoxy)aminocarbonyl]-benzyl; the compound wherein R 22 is 4-[(N-methoxy)aminocarbonyl]-benzyl and R 23 is 4-[(N-methoxy)aminocarbonyl]-benzyl; the compound wherein R 22 is 3-(HOCH 2 CH(OH)CH 2 O)benzyl and R 23 is 3-(HOCH 2 CH(OH)CH 2 O)benzyl; the compound wherein R 22 is 3-(2-hydroxyethoxy)benzyl and R 23 is 3-(2-hydroxyethoxy)benzyl; the compound wherein R 22 is 3-(1,2-dihydroxyethyl)benzyl and R 23 is 4-(1,2-dihydroxyethyl)benzyl; the compound wherein R 22 is 3-aminocarbonylbenzyl and R 23 is 3-(H 2 NC(═NH))benzyl; the compound wherein R 22 is 4-hydroxybenzyl and R 23 is 3-formyl-4-hydroxybenzyl; the compound wherein R 22 is 3-carbomethoxybenzyl and R 23 is 3-(N-methylaminocarbonyl)benzyl; the compound wherein R 22 is 3-(N-methylaminocarbonyl)benzyl and R 23 is 3-(N-methylaminocarbonyl)benzyl; the compound wherein R 22 is benzyl and R 23 is 3-hydroxybenzyl; the compound wherein R 22 is 2-naphthylmethyl and R 23 is 4-hydroxymethylbenzyl; the compound wherein R 22 is 3-(1,2-dihydroxyethyl)benzyl and R 23 is 3-(1,2-dihydroxyethyl)benzyl; the compound wherein R 22 is 4-(1,2-dihydroxyethyl)benzyl and R 23 is 4-(1,2-dihydroxyethyl)benzyl; the compound wherein R 22 is 3-hydroxymethylbenzyl and R 23 is 3-(N-methylaminocarbonyl)benzyl; the compound wherein R 22 is 4-hydroxymethylbenzyl and R 23 is hydrogen; the compound wherein R 22 is 3-(boronic acid)benzyl and R 23 is 3-(boronic acid)benzyl; the compound wherein R 22 is 3-nitrobenzyl and R 23 is 3-benzyloxybenzyl; the compound wherein R 22 is 3-aminobenzyl and R 23 is 3-hydroxybenzyl; the compound wherein R 22 is 3-(N-ethylaminocarbonyl)benzyl and R 23 is 3-(N-ethylaminocarbonyl)benzyl; the compound wherein R 22 is 3-carbomethoxybenzyl and R 23 is 3-(N,N-diethylaminocarbonyl)benzyl; the compound wherein R 22 is 3-carbomethoxybenzyl and R 23 is 3-(N-ethylaminocarbonyl)benzyl; the compound wherein R 22 is 6-hydroxy1-hexyl and R 23 is hydrogen; the compound wherein R 22 is 6-hydroxy1-hexyl and R 23 is 6-hydroxy-1-hexyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is 6-hydroxy-1-hexyl; the compound wherein R 22 is 5-carboxy-1-pentyl and R 23 is 5-carboxy-1-pentyl; the compound wherein R 22 is 3-iodobenzyl and R 23 is 3-iodobenzyl; the compound wherein R 22 is benzyl and R 23 is 2-(hydroxymethyl)-cyclopropylmethyl; the compound wherein R 22 is 3-(thiomethyl)benzyl and R 23 is 3-(thiomethyl)benzyl; the compound wherein R 22 is 3-(methylsulfonyl)benzyl and R 23 is 3-(methylsulfonyl)benzyl; the compound wherein R 22 is 6-hexenyl and R 23 is 6-hexenyl; the compound wherein R 22 is 6-bromo-5-hydroxy-1-hexyl and R 23 is 6-bromo-5-hydroxy-1-hexyl; the compound wherein R 22 is 5-hydroxy-1-pentyl and R 23 is 5-hydroxy-1-pentyl; the compound wherein R 22 is 3-aminobenzyl and R 23 is 4-hydroxymethylbenzyl; the compound wherein R 22 is 3-(H 2 NC(═O)NH)benzyl and R 23 is 3-(H 2 NC(═O)NH)benzyl; the compound wherein R 22 is 3-(N-methylamino)benzyl and R 23 is 3-(N-methylamino)benzyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is 3-aminobenzyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is 3-nitrobenzyl; the compound wherein R 22 is 3-(N,N-dimethylamino)benzyl and R 23 is 3-(N,N-dimethylamino)benzyl; the compound wherein R 22 is 3-nitrobenzyl and R 23 is 4-hydroxymethylbenzyl; the compound wherein R 22 is 3-aminobenzyl and R 23 is 3-(CH 3 NHC(═O)NH)benzyl; the compound wherein R 22 is 3-(CH 3 NHC(═O)NH)benzyl and R 23 is 3-(CH 3 NHC(═O)NH)benzyl; the compound wherein R 22 is 3-(N-methylamino)benzyl and R 23 is 4-hydroxymethylbenzyl; the compound wherein R 22 is 3-((N,N-dimethylaminoglycyl)amino)benzyl and R 23 is 3-((N,N-dimethylaminoglycyl)amino)benzyl; the compound wherein R 22 is 3-((N-methylaminoglycyl)amino)benzyl and R 23 is 3-((N-methylaminoglycyl)amino)benzyl; the compound wherein R 22 is 3-((N,N-dimethylaminoglycyl)amino)benzyl and R 23 is 4-hydroxymethylbenzyl; the compound wherein R 22 is 3-((N-phenylmethoxycarbonylaminoglycyl)amino)benzyl and R 23 is 3-((N-phenylmethoxycarbonylaminoglycyl)amino)benzyl; the compound wherein R 22 is 3-(glycylamino)benzyl and R 23 is 3-(glycylamino)benzyl; the compound wherein R 22 is 3-(glycylamino)benzyl and R 23 is 4-hydroxymethylbenzyl; the compound wherein R 22 is 3-((N-phenylmethoxycarbonylamino-L-alanyl)amino)benzyl and R 23 is 3-((N-phenylmethoxycarbonylamino-L-alanyl)amino)benzyl; the compound wherein R 22 is 3-((N-phenylmethoxycarbonylamino-L-phenylalanyl)amino)benzyl and R 23 is 3-((N-phenylmethoxycarbonylamino-L-phenylalanyl)amino)benzyl; the compound wherein R 22 is 3-(L-alanyl)amino)benzyl and R 23 is 3-(L-alanyl)amino)benzyl; the compound wherein R 22 is 3-(L-phenylalanyl)amino)benzyl and R 23 is 3-(L-phenylalanyl)amino)benzyl; the compound wherein R 22 is 5-hydroxy-1-pentyl and R 23 is hydrogen; the compound wherein R 22 is 5-hydroxy-1-pentyl and R 23 is 2-naphthylmethyl; the compound wherein R 22 is 5-hydroxy-1-pentyl and R 23 is benzyl; the compound wherein R 22 is 5-hydroxy-1-pentyl and R 23 is 4-hydroxymethylbenzyl; the compound wherein R 22 is 6-hydroxy-1-hexyl and R 23 is 2-naphthylmethyl; the compound wherein R 22 is 5-hydroxy-1-pentyl and R 23 is 3-hydroxybenzyl; the compound wherein R 22 is 5-hydroxy-1-pentyl and R 23 is (5-methylsulfonyl)-1-pentyl; the compound wherein R 22 is 5-hydroxy-1-pentyl and R 23 is 5-(CH 3 S(O))-1-pentyl; the compound wherein R 22 is 5-hydroxy-1-pentyl and R 23 is cyclopropylmethyl; the compound wherein R 22 is 5-hydroxy-1-pentyl and R 23 is 5-methoxy-1-pentyl; the compound wherein R 22 is 5-hydroxy-1-pentyl and R 23 is 3-cyanobenzyl; the compound wherein R 22 is 5-hydroxy-1-pentyl and R 23 is 3-carboethoxybenzyl; the compound wherein R 22 is 4-hydroxy-1-hexyl and R 23 is 4-hydroxy-1-hexyl; the compound wherein R 22 is 4-hydroxy-1-hexyl and R 23 is 2-naphthylmethyl; the compound wherein R 22 is 4-oxime-1-hexyl and R 23 is 4-oxime-1-hexyl; the compound wherein R 22 is 5-hydroxy-1-pentyl and R 23 is 3-hydroxymethylbenzyl; the compound wherein R 22 is 6-amino-1-hexyl and R 23 is 4-hydroxymethylbenzyl; the compound wherein R 22 is 3-(N,N-diethylaminocarbonyl)benzyl and R 23 is 3-(N,N-diethylaminocarbonyl)benzyl; the compound wherein R 22 is 3-carbomethoxybenzyl and R 23 is 3-(N,N-diethylaminocarbonyl)benzyl; the compound wherein R 22 is 3-carbomethoxybenzyl and R 23 is 3-(N-ethylaminocarbonyl)benzyl; the compound wherein R 22 is 3-hydroxymethylbenzyl and R 23 is hydrogen; the compound wherein R 22 is 3-hydroxymethylbenzyl and R 23 is 3-(N,N-diethylaminocarbonyl)benzyl; the compound wherein R 22 is 3-hydroxymethylbenzyl and R 23 is 3-(N-ethylaminocarbonyl)benzyl; the compound wherein R 22 is 3-(N-propylaminocarbonyl)benzyl and R 23 is 3-(N-propylaminocarbonyl)benzyl; the compound wherein R 22 is 3-(HO 2 C)benzyl and R 23 is 3-(N-isopropylaminocarbonyl)benzyl; the compound wherein R 22 is 3-(HO 2 C)benzyl and R 23 is 3-(N-propylaminocarbonyl)benzyl; the compound wherein R 22 is 3-(HO 2 C)benzyl and R 23 is benzyl; the compound wherein R 22 is 3-(HO 2 C)benzyl and R 23 is cyclopropylmethyl; the compound wherein R 22 is 4-hydroxymethylbenzyl and R 23 is 3-(HO 2 C)benzyl; the compound wherein R 22 is 3-hydroxymethylbenzyl and R 23 is 3-pyridinylmethyl; the compound wherein R 22 is 4-hydroxymethylbenzyl and R 23 is 3-aminocarbonylbenzyl; the compound wherein R 22 is 3-aminobenzyl and R 23 is 2-naphthylmethyl; the compound wherein R 22 is cyclopropylmethyl and R 23 is 3-aminocarbonylbenzyl; the compound wherein R 22 is 3-aminocarbonylbenzyl and R 23 is hydrogen; the compound wherein R 22 is 3-hydroxymethylbenzyl and R 23 is 3-(N-ethylaminocarbonyl)benzyl; the compound wherein R 22 is 3-hydroxymethylbenzyl and R 23 is 3-(N-methylamino)benzyl; the compound wherein R 22 is 3-(N-methylamino)benzyl and R 23 is 2-naphthylmethyl; the compound wherein R 22 is 4-formylbenzyl and R 23 is 4-hydroxymethylbenzyl; the compound wherein R 22 is 3-(1-hydroxy-1-ethyl)benzyl and R 23 is 3-(1-hydroxyethyl)benzyl; the compound wherein R 22 is 3-pyridinylmethyl and R 23 is 4-hydroxymethylbenzyl; the compound wherein R 22 is 3-(N-imidazolylmethyl)benzyl and R 23 is 3-(N-imidazolylmethyl)benzyl; the compound wherein R 22 is 3-(2,2-dimethyl-1-propionyl)benzyl and R 23 is 3-(2,2-dimethyl-1-propionyl)benzyl; the compound wherein R 22 is 3-(2,2,2-trifluoro-1-hydroxyethyl)benzyl and R 23 is 3-(2,2,2-trifluoro-1-hydroxyethyl)benzyl; the compound wherein R 22 is 3-(2-imidazolyl-C(═O))benzyl and R 23 is 3-(2-imidazolyl-C (═O))benzyl; the compound wherein R 22 is 3-(3-hydroxy-1-propyn-1-yl)benzyl and R 23 is 3-(3-hydroxy-1-propyn-1-yl)benzyl; the compound wherein R 22 is 3-(2,2,2-trifluoroacetyl)benzyl and R 23 is 3-(2,2,2-trifluoroacetyl)benzyl; the compound wherein R 22 is 3-propionylbenzyl and R 23 is 3-propionylbenzyl; the compound wherein R 22 is 3-(4-pyrazolyl)benzyl and R 23 is 3-(4-pyrazolyl)benzyl; the compound wherein R 22 is 3-(CH 3 CH 2 C(═N-OH))benzyl and R 23 is 3-(CH 3 CH 2 C(═N--OH)benzyl; the compound wherein R 22 is 3-sulfonamidobenzyl and R 23 is 3-sulfonamidobenzyl; the compound wherein R 22 is 3-(CF 3 CH 2 C(═N-OH))benzyl and R 23 is 3-(CF 3 CH 2 C(═N-OH))benzyl; the compound wherein R 22 is 4-fluoromethylbenzyl and R 23 is 4-fluoromethylbenzyl; the compound wherein R 22 is 4-(1-hydroxyethyl)benzyl and R 23 is 4-(1-hydroxyethyl)benzyl; and the compound wherein R 22 is 3-(5-methyl-1,2,3-oxadiazolyl)benzyl and R 23 is 3-(5-methyl-1,2,3-oxadiazolyl)benzyl; the compound wherein R 22 is 3-(H 2 NC(═NOH)benzyl and R 23 is 3-(H 2 NC(═NOH)benzyl; the compound wherein R 22 is 3-(H 2 NC(═NOH)-4-fluorobenzyl and R 23 is 3-(H 2 NC(═NOH)-4-fluorobenzyl; the compound wherein R 22 is 5-benzotriazolylmethyl and R 23 is 5-benzotriazolylmethyl; the compound wherein R 22 is 5-benzimidazolylmethyl and R 23 is 5-benzimidazolylmethyl; the compound wherein R 22 is 5-benzimidazolylmethyl and R 23 is 5-benzimidazolylmethyl; the compound wherein R 22 is 5-benzotriazolylmethyl and R 23 is 4-hydroxymethylbenzyl; the compound wherein R 22 is 5-benzotriazolylmethyl and R 23 is 3-(3-pyrazolyl)benzyl; the compound wherein R 22 is 5-indazolylmethyl and R 23 is 5-indazolylmethyl; the compound wherein R 22 is 3-chloro-5-indazolylmethyl and R 23 is 3-chloro-5-indazolylmethyl; the compound wherein R 22 is 3-methylamino-5-indazolylmethyl and R 23 is 3-methylamino-5-indazolylmethyl; the compound wherein R 22 is 3-ethylamino-5-indazolylmethyl and R 23 is 3-ethylamino-5-indazolylmethyl; the compound wherein R 22 is 6-indazolylmethyl and R 23 is 6-indazolylmethyl; the compound wherein R 22 is 3-amino-5-benzisoxazolylmethyl and R 23 is 3-amino-5-benzisoxazolylmethyl. the compound wherein R 4 is 4-aminobenzyl, R 7 is 2-aminobenzyl, R 22 and R 23 are cyclopropylmethyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3-hydroxybenzyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are cyclopropylmethyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 4-hydroxymethylbenzyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3-aminocarbonylbenzyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3-acetylbenzyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3-butyrylbenzyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3-hydroxymethylbenzyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3- (CH 3 C (═N-OH)benzyl; and the compound wherein R 4 and R 7 are 3-methoxybenzyl, R 22 and R 23 are benzyl. the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3- (H 2 NC(═NOH) benzyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3- (H 2 NC(═NOH) -4-fluorobenzyl; the compound wherein R 4 and R 7 are 3-methoxybenzyl, R 22 and R 23 are cyclopropylmethyl; the compound wherein R 4 and R 7 are 3-methoxybenzyl, R 22 and R 23 are 4-hydroxymethylbenzyl; the compound wherein R 4 and R 7 are 3-methoxybenzyl, R 22 and R 23 are 3-methoxybenzyl; the compound wherein R 4 and R 7 are 3-hydroxybenzyl, R 22 and R 23 are 3-hydroxybenzyl.. the compound wherein R 4 and R 7 are 4-methoxybenzyl, R 22 and R 23 are cyclopropylmethyl; the compound wherein R 4 and R 7 are 4-methoxybenzyl, R 22 and R 23 are benzyl; the compound wherein R 4 and R 7 are 4-methoxybenzyl, R 22 and R 23 are 2-naphthylmethyl; the compound wherein R 4 and R 7 are 4-methoxybenzyl, R 22 and R 23 are 4-hydroxymethylbenzyl; the compound wherein R 4 and R 7 are 4-hydroxybenzyl, R 22 and R 23 are benzyl; the compound wherein R 4 and R 7 are 4-methoxybenzyl, R 22 and R 23 are allyl; the compound wherein R 4 and R 7 are 4-(2- hydroxyethoxy)benzyl, R 22 and R 23 are benzyl; the compound wherein R 4 and R 7 are 4-(2- morpholinylethoxy)benzyl, R 22 and R 23 are benzyl; the compound wherein R 4 and R 7 are 3- (H 2 NC(═O) CH20) benzyl, R 22 and R 23 are n-butyl; the compound wherein R 4 and R 7 are 3,4- difluorobenzyl, R 22 and R 23 are 3-hydroxymethylbenzyl; the compound wherein R 4 and R 7 are 3,4- difluorobenzyl, R 22 and R 23 are 4-hydroxymethylbenzyl; the compound wherein R 4 and R 7 are 3,4- difluorobenzyl, R 22 and R 23 are 3-(H 2 NC(═O))benzyl; the compound wherein R 4 and R 7 are 3,4- difluorobenzyl, R 22 and R 23 are 3-(H 2 NC(═NOH))benzyl; the compound wherein R 4 and R 7 are 2- naphthylmethyl, R 22 and R 23 are benzyl; the compound wherein R 4 and R 7 are 2- naphthylmethyl, R 22 and R 23 are cyclopropylmethyl; the compound wherein R 4 and R 7 are 2-thienylmethyl, R 22 and R 23 are cyclopropylmethyl; the compound wherein R 4 and R 7 are 2-thienylmethyl, R 22 and R 23 are 3- (H 2 NC(═NOH))benzyl; the compound wherein R 4 and R 7 are 4- methylthiobenzyl, R 22 and R 23 are benzyl; the compound wherein R 4 and R 7 are isopropyl, R 22 and R 23 are n-hexyl
34. A composition of claim 1 wherein said compound of Formula (I)is a compound of the formula: ##STR21## or a pharmaceutically acceptable salt or prodrug form thereof wherein: R 4 and R 7 are independently selected from: benzyl, fluorobenzyl, pyrrolylmethyl, methoxybenzyl, isobutyl, nitrobenzyl aminobenzyl, hydroxybenzyl, or thienylmethyl; and R 22 and R 23 are independently selected from: hydrogen, allyl, methyl, ethyl, propyl, cyclopropylmethyl, n-butyl, i-butyl, CH 2 CH═C(CH 3 ) 2 , pyridinylmethyl, methallyl, n-pentyl, i-pentyl, hexyl, benzyl, isoprenyl, propargyl, picolinyl, methoxyethyl, cyclohexylmethyl, dimethyl-butyl, ethoxyethyl, methyl-oxazolinylmethyl, naphthylmethyl, methyloxazolinylmethyl, vinyloxyethyl, pentafluorobenzyl, quinolinylmethyl, carboxybenzyl, chloro-thienyl, benzyloxybenzyl, phenylbenzyl, adamantylethyl, cyclopropylmethoxybenzyl, methoxybenzyl, methylbenzyl, ethoxybenzyl, hydroxybenzyl, hydroxymethylbenzyl, aminobenzyl, formylbenzyl, cyanobenzyl, cinnamyl, allyloxybenzyl, fluorobenzyl, difluorobenzyl, chlorobenzyl, chloromethylbenzyl, fluoromethylbenzyl, iodobenzyl, bromobenzyl, cyclobutylmethyl, formaldoximebenzyl, cyclopentylmethyl, nitrobenzyl, (H 2 NC(═O))-benzyl, carbomethoxybenzyl, carboethoxybenzyl, tetrazolylbenzyl, and dimethylallyl, aminomethylbenzyl, (O-benzyl-formaldoxime)benzyl, (O-methyl-formaldoxime)benzyl, (CH 3 O 2 CO)-benzyl, (HOCH 2 CH 2 N═CH)-benzyl, N-benzylaminocarbonylbenzyl, N-methylaminobenzyl, N-ethylaminobenzyl, N-ethylaminomethylbenzyl, acetylbenzyl, acetoxybenzyl, N-hydroxylaminobenzyl, phenylmethyl-boronic acid, N-hydroxylaminomethylbenzyl, (hydroxyl)ethylbenzyl, (CH 3 C(═NOH))-benzyl, (H 2 NNHC(═O))-benzyl, (H 2 NC(═O)NHN═CH)-benzyl, (CH 30 NHC(═O))-benzyl, (HONHC(═O))-benzyl, (CH 3 NHC(═O))-benzyl, N,N-dimethylaminocarbonylbenzyl, (HOCH 2 CH (OH)CH 2 O)-benzyl, hydroxyethoxybenzyl (oxazolidinyl)-benzyl, (hydroxyl)hexyl, hexenyl, (hydroxy)octyl, (hydroxyl)pentyl, (carboxy)pentyl, (carbomethoxy)pentyl, (methylthio)benzyl, (methylsulfonyl)benzyl, N,N-dimethylaminomethylbenzyl, N-methylaminomethylbenzyl, glycylaminobenzyl, N,N-dimethylglycylaminobenzyl, alanylaminobenzyl, (N-phenylmethoxycarbonyl)alanylaminobenzyl, phenylalanylaminobenzyl, (N-phenylmethoxycarbonyl) phenylalanylaminobenzyl, (CH 3 CH 2 NHC(═O))-benzyl, N,N-diethylaminocarbonylbenzyl, N-ethylaminocarbonylbenzyl, N-propylaminocarbonylbenzyl, N,N-diisopropylaminocarbonylbenzyl, N,N-di-n-propylaminocarbonylbenzyl, (hydroxypropynyl)benzyl, (imidazolyl-C(═O))-benzyl, (pyrazolyl-C(═O))-benzyl, (pyridylmethylaminocarbonyl)benzyl, (oxadiazolidinonyl)benzyl, trifluoroacetylbenzyl, (pyrazolyl)benzyl, (H 2 NSO 2 )-benzyl, dihydroxyethylbenzyl, (MeHNC(═O)NH)-benzyl, (H 2 NC(═O)NH)-benzyl, (HC(═O)NH)-benzyl, methanesulfonylpentyl, methoxypentyl, N-formyl-N-methylaminobenzyl, acetylaminobenzyl, propionylbenzyl, butyrylbenzyl, (CH 3 CH 2 C(═NOH))-benzyl, (trifluorohydroxyethyl)benzyl, (CF 3 C(═NOH))-benzyl, (N-methylglycyl)aminobenzyl, ((4-morpholino)ethyl)aminocarbonylbenzyl, (N,N-dimethylaminoethyl)aminocarbonylbenzyl, (N,N-diethylaminoethyl)aminocarbonylbenzyl, (4 -methylpiperaz in-1-ylethyl)aminocarbonylbenzyl, (benzyl-NHC(═O)O)benzyl, (CH 3 NHC(═O)O)benzyl, (NH 2 C(═O)CH 2 O)benzyl, (NH 2 C(═NH))benzyl, ((N-phenylmethoxycarbonyl)glycylamino)benzyl, (imidazolylmethyl)benzyl, ((CH 3 ) 3 C-C(═O))benzyl, (N-methyl-N-ethylaminoethyl)aminocarbonylbenzyl, (pyrrolidinylethyl)aminocarbonylbenzyl, or (piperidinylethyl)aminocarbonylbenzyl, (H 2 NC(═NOH))benzyl, (H 2 NC(═NOH))fluorobenzyl, benzimidazolylmethyl, benzotriazolylmethyl, indazolylmethyl, benzoxazolinylmethyl, benzisoxazolylmethyl, thienylmethyl, furylmethyl.
35. A composition of claim 1 wherein said compound of Formula (I) is a compound of the formula: ##STR22## selected from the group consisting of: the compound wherein R 4 and R 7 are isobutyl, R 22 and R 23 are cyclopropylmethyl; the compound wherein R 4 and R 7 are isobutyl, R 22 and R 23 are allyl; the compound wherein R 4 is 4-nitrobenzyl, R 7 is 2-nitrobenzyl, R 22 and R 23 are cyclopropylmethyl; the compound wherein R 4 and R 7 are 4-nitrobenzyl, R 22 and R 23 are cyclopropylmethyl; the compound wherein R 4 is 4-nitrobenzyl, R 7 is 2-nitrobenzyl, R 22 and R 23 are n-butyl; the compound wherein R 4 is 4-aminobenzyl, R 7 is 2-aminobenzyl, R 22 and R 23 are cyclopropylmethyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3-hydroxybenzyl; the compound wheren R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are cyclopropylmethyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 4-hydroxymethylbenzyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3-aminocarbonylbenzyl; The compound wheien R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3-acetylbenzyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3-butyrylbenzyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3-hydroxymethylbenzyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3-(CH 3 C(═N-OH)benzyl; and the compound wherein R 4 and R 7 are 3-methoxybenzyl, R 22 and R 23 are benzyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3-(H 2 NC(═NOH)benzyl; the compound wherein R 4 and R 7 are 4-fluorobenzyl, R 22 and R 23 are 3-(H 2 NC(═NOH)-4-fluorobenzyl; the compound wherein R 4 and R 7 are 3-methoxybenzyl, R 22 and R 23 are cyclopropylmethyl; the compound wherein R 4 and R 7 are 3-methoxybenzyl, R 22 and R 23 are 4-hydroxymethylbenzyl; the compound wherein R 4 and R 7 are 3-methoxybenzyl, R 22 and R 23 are 3-methoxybenzyl; the compound wherein R 4 and R 7 are 3-hydroxybenzyl, R 22 and R 23 are 3-hydroxybenzyl; the compound wherein R 4 and R 7 are 3-hydroxybenzyl, R 22 and R 23 are cyclorpropylmethy; the compound wherein R 4 and R 7 are 4-methoxybenzyl, R 22 and R 23 are benzyl; the compound wherein R 4 and R 7 are 4-methoxybenzyl, R 22 and R 23 are 2-naphthylmethyl; the compound wherein R 4 and R 7 l are 4-methoxybenzyl, R 22 and R 23 are 4-hydroxymethylbenzyl; the compound wherein R 4 and R 7 are 4-hydroxybenzyl, R 22 and R 23 are benzyl; the compound wherein R 4 and R 7 are 4-methoxybenzyl, R 22 and R 23 are allyl; the compound wherein R 4 and R 7 are 4-(2-hydroxyethoxy) benzyl, R 22 and R 23 are benzyl; the compound wherein R 4 and R 7 are 4-(2-morpholinylethoxy)benzyl, R 22 and R 23 are benzyl; the compound wherein R 4 and R 7 are 3-(H 2 NC(═O)CH 2 O)benzyl, R 22 and R 23 are n-butyl; the compound wherein R 4 and R 7 are 3,4-difluorobenzyl, R 22 and R 23 are 3-hydroxymethylbenzyl; the compound wherein R 4 and R 7 are 3,4-difluorobenzyl, R 22 and R 23 are 3-(H 2 NC(═O)benzyl; the compound wherein R 4 and R 7 are 2-naphthylmethyl, R 22 and R 23 are benzyl; the compound wherein R 4 and R 7 are 2-naphthylmethyl, R 22 and R 23 are cyclopropylmethyl; the compouhd wherein R 4 and R 7 are 2-thienylmethyl, R 22 and R 23 are cyclopropylmethyl; the compound wherein R 4 and R 7 are 4-methylthiobenzyl, R 22 and R 23 are benzyl; the compound wherein R 4 and R 7 are isopropyl, R 22 and R 23 are n-hexyl.
36. A composition of claim 1 wherein said compound of Formula (I)is [4R-(4α, 5α, 6β, 7β)]-hexahydro-5,6-bis(hydroxy)-1,3-bis([(4-hydroxymethyl)phenyl]methyl)-4,7-bis(phenylmethyl)-2H-1,3-diazepin-2-one.
37. A composition of claim 1 wherein said compound of Formula (I) is [4R-(4α, 5α, 6β, 7β)]-hexahydro-5,6-bis(hydroxy)-1,3-bis([(4-hydroxymethyl)phenyl]methyl)-4,7-bis(phenylmethyl)-2H-1,3-diazepin-2-one and said vehicle comprises a mixture of fatty acid esters of glycerol and fatty acid esters of polyethylene glycol having the characteristics set forth in Table A.
38. A pharmaceutical kit comprising: (a) a therapeutically effective amount of compound of the Formula (I): ##STR23## or a pharmaceutically acceptable salt or prodrug form thereof, wherein: R 4 and R 7 are independently selected from the following groups: hydrogen; C 1 -C 8 alkyl substituted with 0-3 R 11 ; C 2 -C 8 alkenyl substituted with 0-3 R 11 ; C 2 -C 8 alkynyl substituted with 0-3 R 11 ; a C 3 -C 14 carbocyclic ring system substituted with 0-3 R 11 or 0-3 R 12 ; a 5- to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-2 R 12 ; or --OR 13 ; --SR 13 ; CO 2 R 13 ; R 4A and R 7A are independently selected from the following groups: hydrogen; C 1 -C 4 alkyl substituted with 0-6 halogen or 0-3 C 1 -C 2 alkoxy; benzyl substituted with 0-6 halogen or 0-3 C 1 -C 2 alkoxy; or --OR 13 ; --SR 13 ; CO 2 R 13 ; R 4 and R 4A can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R 12 ; R 7 and R 7A can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R 12 ; n is 0; R 5 is selected from H; halogen; C 1 -C 6 alkyl substituted with 0-3 R 11 ; --N( R 20 ) 2 ; --SR 20 ; or --OR 20 , --N 3 ; R 6 is independently selected from: hydrogen, halogen, C 1 -C 6 alkyl substituted with 0-3 R 11 , --N(R 20 ) 2 , --SR 20 , or --OR 21 , --N 3 ; R 5 and R 6 can alternatively join to form an epoxide or aziridine ring; --OCH 2 SCH 2 O--; --OS(═O)O--; --OC(═O)O--; --OCH 2 O--; --OC(═S)O--; --OC(═O)C(═O)O--; --OC(CH 3 ) 2 O--; --OC((CH 2 ) 3 NH 2 )(CH 3 )O--; --OC(OCH 3 )(CH 2 CH 2 CH 3 )O--; --OS(═O)O--; --NHC(═O)NH--; --OC(═O)NH--; --NHC(═O)O--; --NHCH 2 O--; --OCH 2 NH--; --NHC(═S)O--; --OS(═O)NH--; --NHC(═O)C(═O)O--; --OC(═O)C(═O)NH--; --NHC(═O)C(═O)NH--; --OC(CH 3 ) 2 O--; --NHC(CH 3 ) 2 O--; --OC(CH 3 ) 2 NH- 13 or any group that, when administered to a mammalian subject, cleaves to form a free dihydroxyl or diamino or hydroxyl and amino; R 5a is selected from hydrogen, halogen, C 1 -C 6 alkyl, --N(R 20 ) 2 , --SR 20 , or --OR 20 ; R 6a is selected from: hydrogen, halogen, C 1 -C 6 alkyl, --N(R 20 ) 2 , --SR 20 or --OR 21 ; R 5 and R 5a can alternatively join to form ═O, ═S, or a ketal ring; R 6 and R 6a can alternatively join to form ═O, ═S, or a ketal ring; R 20 and R 21 are independently selected from: hydrogen; C 1 -C 6 alkyl substituted with 0-3 R 11 ; C3-C 6 alkoxyalkyl substituted with 0-3 R 11 ; C 1 -C 6 alkylcarbonyl substituted with 0-3 R 11 ; C 1 -C 6 alkoxycarbonyl substituted with 0-3 R 11 ; C 1 -C 6 alkylaminocarbonyl substituted with 0-3 R 11 ; benzoyl substituted with 0-3 R 12 ; phenoxycarbonyl substituted with 0-3 R 12 ; phenylaminocarbonyl substituted with 0-3 R 12 ; or any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl, amino or sulfhydryl; R 11 is selected from one or more of the following: H, keto, halogen, cyano, --CH 2 NR 13 R 14 , --NR 13 R 14 , --CO 2 R 13 , --OC(═O)R 13 , --OR 13 , C 2 -C 6 alkoxyalkyl, --S(O) m R 13 , --NHC(═NH)NHR 13 , --C(═NH)NHR 13 , --C(═O)NR 13 R 14 , --NR 14 C(═O)R 13 , ═NOR 14 , --NR 14 C(═O)OR 14 , --OC(═O)NR 13 R 14 , --NR 13 C(═O)NR 13 R 14 , --NR 14 SO 2 NR 13 R 14 , --NR 14 SO 2 R 13 , --SO 2 NR 13 R 14 , --OP(O)(OR 13 ) 2 , C 1 -alkyl, C 2 -C 4 alkenyl, C 3 -C 10 cycloalkyl, C 3 -C 6 cycloalkylmethyl, benzyl, phenethyl, phenoxy, benzyloxy, nitro, C 7 -C 10 arylalkyl, hydroxamic acid, hydrazide, boronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, C 1 -C 4 alkyl substituted with --NR 13 R 14 , C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, pyridylcarbonyloxy, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --OCH 2 CO 2 H, 2-(1-morpholino)ethoxy, azido, or --(R 14 )═N(OR 14 ); - 3amino acids linked together via amide bonds, said amino acid being linked via the amine or carboxylate terminus; C 3 -C 10 cycloalkyl substituted with 0-2 R 12 ; C 1 -C 4 alkyl substitued with 0-2 R 12 aryl(C 1 -C 3 alkyl)substituted with 0-2 R 12 ; C 2 -C 6 alkoxyalkyl, substituted with 0-2 R 12 ; C 1 -C 4 alkylcarbonyloxy substituted with 0-2 R 12 , C 6 -C 10 arylcarbonyloxy substituted with 0-2 R 12 , a C 5 -C 14 carbocyclic residue substituted with 0-3 R 12 ; or a 5-to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-3 R 12 ; R 11A is selected from one or more of the following: H, keto, halogen, cyano, --CH 2 NH 2 , --NH 2 , --NHMe, --CO 2 H, --OC(═O)(C 1 -C 3 alkyl), --OH, C 2 -C 6 alkoxyalkyl, --C(═O)NH 2 , --OC(═O)NH 2 , --NHC(═O)NH 2 , --SO 2 NH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 3 -C 10 cycloalkyl, C 3 -C 6 cycloalkylmethyl, benzyl, phenethyl, phenoxy, benzyloxy, nitro, C 7 -C 10 arylalkyl, hydroxamic acid, hydrazide, boronic acid, C 3 -C 6 cycloalkoxy, C 1 -C 4 alkyl substituted with --NH 2 , C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --OCH 2 CO 2 H, 2-(1-morpholino)ethoxy, azido, aryl(C 1 -C 3 alkyl), a C 5 -C 14 carbocyclic residue; a 5-to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system substituted with 0-3 R 12A ; R 12 , when a substituent on carbon, is selected from one or more of the following: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, C 7 -C 10 arylalkyl, C 1 -C 4 alkoxy, --CO 2 H, hydroxamic acid, hydrazide, oronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, --OR 13 , C 1 -C 4 alkyl substituted with --NR 13 R 14 , --NR 13 R 14 , C 2 -C 6 alkoxyalkyl optionally substituted with --Si(CH 3 ) 3 ,, C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 3 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --S(O) m R 13 , --SO 2 NR 13 R 14 , --NHSO 2 R 14 , --OCH 2 CO 2 R 13 , 2-(1-morpholino)ethoxy, or --C(R 14 )═N(OR 14 ); or a 5-or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur; or R 12 may be a 3-or 4-carbon chain attached to adjacent carbons on the ring to form a fused 5-or 6-membered ring, said 5-or 6-membered ring being optionally substituted on the aliphatic carbons with halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, or --NR 13 R 14 ; or, when R 12 is attached to a saturated carbon atom, it may be ═O or ═S; or when R 12 is attached to sulfur it may be ═O; R 12 , when a substituent on nitrogen, is selected from one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, --CH 2 NR 13 R 14 , --NR 13 R 14 , C 2 -C 6 alkoxyalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxycarbonyl, --CO 2 H, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, or --C(R 14 )═N(OR 14 ); R 12A , when a substituent on carbon, is selected from one or more of the following: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, C 7 -C 10 arylalkyl, C 1 -C 4 alkoxy, --CO 2 H, hydroxamic acid, hydrazide, boronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, --OR 13 , C 1 -C 4 alkyl substituted with --NH 2 , --NH 2 , --NHMe, C 2 -C 6 alkoxyalkyl optionally substituted with --Si(CH 3 ) 3 , C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --S(O) m Me, --SO 2 NH 2 , --NHSO 2 Me, --OCH 2 CO 2 R 13b , 2 -(1-morpholino)ethoxy, --C(═NOH)NH 2 ; or a 5-or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur; or R 12A may be a 3-or 4-carbon chain attached to adjacent carbons on the ring to form a fused 5-or 6-membered ring, said 5-or 6-membered ring being optionally substituted on the aliphatic carbons with halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, or --NH 2 ; or, when R 12A is attached to a saturated carbon atom or sulfur, it may be ═O or ═S; R 12A , when a substituent on nitrogen, is selected from one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, --CH 2 NH 2 , --NH 2 , C 2 -C 6 alkoxyalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxycarbonyl, --CO 2 H, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, --C(═NOH)NH 2 ; R 13 is selected from: H; phenyl substituted with 0-3 R 11A ; benzyl substituted with 0-3 R 11A ; C 1 -C 6 alkyl substituted with 0-3 R 11A ; C 2 -C 4 alkenyl substituted with 0-3 R 11A ; C 1 -C 6 alkylcarbonyl substituted with 0-3 R 11A ; C 1 -C 6 alkoxycarbonyl substituted with 0-3 R 11A ; C 1 -C 6 alkylaminocarbonyl substituted with 0-3 R 11A ; C 3 -C 6 alkoxyalkyl substituted with 0-3 R 11A ; an amine protecting group when R 13 is bonded to N; or a hydroxy protecting group when R 13 is bonded to O; R 14 is hydrogen, hydroxy, CF 3 ; C 1 -C 6 alkyl substituted with 0-3 groups selected from OH, C 1 -C 4 alkoxy, halogen, NH 2 , C 1 -C 6 alkoxy; NH 2 ; --NH(C 1 -C 4 alkyl), C 2 -C 6 alkenyl; phenyl, benzyl, an amine protecting group when R 14 is bonded to N, or a hydroxy protecting group when R 14 is bonded to O; R 13 can alternatively join to form --(CH 2 ) 4 --, --(CH 2 ) 5 --, --(CH 2 ) 2 N, N(R 15 )CH 2 CH 2 --, or --CH 2 CH 2 OCH 2 CH 2 --; R 15 is H or CH 3 ; m is 0, 1 or 2; W is --N(R 22 )C(═Z)N(R 23 )--; wherein: Z is O; R 22 and R 23 are independently selected from the following: hydrogen; C 1 -C 8 alkyl substituted with 0-3 R 31 ; C 2 -C 8 alkenyl substituted with 0-3 R 31 ; C 2 -C 8 alkynyl substituted with 0-3 R 31 ; a C 3 -C 14 carbocyclic ring system substituted with 0-5 R 31 or R 32 ; a 5-to 10-membered heterocyclic ring system containing 1 to 4 to heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-5 R 32 ; --OR 22a ; or --N(R 22a )(R 22b ); R 22a and R 22b are independently selected from the following: hydrogen; C 1 -C 8 alkyl substituted with 0-3 R 31 ; C 2 -C 8 alkenyl substituted with 0-3 R 31 ; C 2 -C 8 alkynyl substituted with 0-3 R 31 ; a C 3 -C 14 carbocyclic ring system substituted with 0-5 R 31 or R 32 ; a 5-to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-5 R 32 ; alternatively, R 22 can join with R 4 or R 4A to form a 5-or 6-membered fused heterocyclic ring or carbocyclic ring substituted with 0-2 R 12 , said heterocyclic ring containing 1-3 heteroatoms independently selected from N, S, or O; or alternatively, R 23 can join with R 7 or R 7A to form a 5-or 6-membered fused heterocyclic ring or carbocyclic ring substituted with 0-2 R 12 , said heterocyclic ring containing 1-3 heteroatoms independently selected from N, S, or O; or alternatively, R 22 or R 23 can join with R 5 or R 6 to form a 0- to 7-membered bridge to form a carbocyclic or heterocyclic ring, said bridge being substituted with 0-2 R 12 and said bridge containing 0-3 heteroatoms independently selected from N, S, or O (i.e., a O-membered bridge is formed when R 22 or R 23 are taken together with R 5 or R 6 to form a direct bond); or alternatively R23 can join with R7A to form a direct bond; or alternatively R22 can join with R4A to form a direct bond; R 31 is selected from one or more of the following: keto, halogen, cyano, --CH 2 NR 13 R 14 , --NR 13 R 14 , --CO 2 R 13 , --C(═O)R 11 , --OC(═O)R 13 , --OR 13 , C 2 -C 6 alkoxyalkyl, --S(O)m R 13 , --NR 13 C(═S)NR 13 R 14 , --NR 14 SO 2 NR 13 R 14 , --NR 13 SO 2 R 13 , --NHC(═NH)NHR 13 , --C(═NH)NHR 13 , --C(═O)NR 13 R 14 , --NR 13 C(═O)R 13 , ═NOR 13 , --NR 14 C(═O)OR 14 , --OC(═O)NR 13 R 14 , --NR 13 C(═O)NR 13 R 14 , --SO 2 NR 13 R 14 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 3 -C 10 cycloalkyl, C 3 -C 6 cycloalkylmethyl, benzyl, phenethyl, phenoxy, benzyloxy, nitro, C 7 -C 10 arylalkyl, hydroxamic acid, hydrazide, oxime, boronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, C 1 -C 4 alkyl substituted with --NR 13 R 14 , C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --OCH 2 CO 2 R 13 , 2-(1-morpholino)ethoxy, azido, --C(R 14 )═N(OR 14 ); or - 3amino acids, linked together via amide bonds, said amino acid being linked via the amine or carboxylate terminus; a C 5 -C 14 carbocyclic residue substituted with 0-5 R 32 ; or a 5-to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-2 R 32 ; R 32 , when a substituent on carbon, is selected from one or more of the following: phenethyl, phenoxy, C 3 -C 10 cycloalkyl, C 3 -C 6 cycloalkylmethyl, C 7 -C 10 arylalkyl, hydrazide, oxime, boronic acid, C 2 -C 6 alkoxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 alkylcarbonyloxy, --NHSO 2 R 14 , benzyloxy, halogen, 2-(1-morpholino)ethoxy, --CO 2 R 13 , hydroxamic acid, --CONR 13 NR 13 R 14 , cyano, boronic acid, sulfonamide, --CHO, C 3 -C 6 cycloalkoxy, --NR 13 R 14 , --C(R 14 )═N(OR 14 )NO 2 , OR 13 ,--NR 40 R 41 , --SO m R 13 , --SO m NR 13 R 14 , --C(═O)NR 13 R 14 , --OC(═O)NR 13 R 14 , --C(═O)R 11 , --OC(═O)R 11 , --OCO 2 R 13 , phenyl, --C(═O)NR 13 (C 1 -C 4 alkyl)-NR 13 R 14 , --C(═O)NR 40 R 41 , C 1 -C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 1 -C 4 haloalkynyl, C 1 -C 4 haloalkenyl, or --C(═O)NR 13 C(R 11 ) 2 NR 13 R 14 ; -- --C(═O)NR 13 C(R 11 ) 2 NR 13 NR 14 ; --C(═O)NR 13 C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O)NR 13 -(C 1 -C 4 alkyl)--NR 13 CO 2 R 13 ; --C(═O)N(R 13 )-(C 1 -C 4 alkyl)-R 11 ; or --C(═O)C(R 11 ) 2 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 NR 14 ; --C(═O)C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 R 14 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 CO 2 R 13 ; or C 1 -C 4 alkoxy substituted with 0-4 groups selected from: R 11 , C 3-C 6 cycloalkyl, --CO 2 R 13 , --C(═O)NR 13 R 14 , --NR 13 R 14 or OH; C 1 -C 4 alkyl substituted with 0-4 groups selected from: R 11 ═NR 14 , ═NNR 13 C(═O)NR 13 R 14 or --NR 13 R 14 , ═NNR 13 C(═O)OR 13 ,; C 2 -C 4 alkenyl substituted with 0-4 R 11 ; C 2 -C 4 alkynyl substituted with 0-4 R 11 ; a 5-or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, substituted with 0-2 R 12 ; or R 32 may be a 3-or 4-carbon chain attached to adjacent carbons on the ring to form a fused 5-or 6-membered ring, said 5-or 6-membered ring being optionally substituted on the aliphatic carbons with halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, or --NR 13 R 14 ; or, when R 32 is attached to a saturated carbon atom, it may be ═O or ═S, ═NOH; or when R 32 is attached to sulfur it may be ═O; R 32 , when a substituent on nitrogen, is selected from one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, --CH 2 NR 13 R 14 , --NR 13 R 14 , C 2 -C 6 alkoxyalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxycarbonyl, --CO 2 H, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, or --C(R 14 )═N (OR 14 ); R 40 is selected from: H or C 1 -C 3 alkyl; R 41 is selected from: --C(═O)NR 13 R 14 ; --C(═O)NR 13 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O)H; --C(═O)R 11 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 R 14 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 CO 2 R 13 ; - 3amino acids linked together via amide bonds, and linked to the N atom via the carboxylate terminus; provided that: R 4 , R 4A , R 7 and R 7A are not all hydrogen; when R 4 , R 4A are hydrogen, R 22 and (b) a vehicle comprising a fatty acid ester of glycerol, a fatty acid ester of polyethylene glycol, or mixture thereof, wherein said vehicle has a hydrophil-lipophil balance of at least about 10.
39. A pharmaceutical kit of claim 38 further comprising conventional kit components.
40. A pharmaceutical dosage form for oral administration comprising a gelatin capsule containing in the hollow interior thereof, a pharmaceutical composition comprising: (a) a therapeutically effective amount of compound of the Formula (I): ##STR24## or a pharmaceutically acceptable salt or prodrug form thereof, wherein: R 4 and R 7 are independently selected from the following groups: hydrogen; C 1 -C 8 alkyl substituted with 0-3 R 11 ; C 2 -C 8 alkenyl substituted with 0-3 R 11 ; C 2 -C 8 alkynyl substituted with 0-3 R 11 ; a C 3 -C 14 carbocyclic ring system substituted with 0-3 R 11 or 0-3 R 12 ; a 5-to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-2 R 12 ; or --OR 13 ; --SR 13 ; CO 2 R 13 ; R 4A and R 7A are independently selected from the following groups: hydrogen; C 1 -C 4 alkyl substituted with 0-6 halogen or 0-3 C 1 -C 2 alkoxy; benzyl substituted with 0-6 halogen or 0-3 C 1 -C 2 alkoxy; or --OR 13 ; --SR 13 ; CO 2 R 13 ; R 4 and R 4A can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R 12 ; R 7 and R 7A can alternatively join to form a 5-membered carbocyclic ring substituted with 0-2 R 12 ; n is 0; R 5 is selected from H; halogen; C 1 -C 6 alkyl substituted with 0-3 R 11 ; --N(R 20 ) 2 ; --SR 20 ; or --OR 20 , --N 3 ; R 6 is independently selected from: hydrogen, halogen, C 1 -C 6 alkyl substituted with 0-3 R 11 , --N(R 20 ) 2 , --SR 20 , or --OR 21 , --N 3 ; R 5 and R 6 can alternatively join to form an epoxide or aziridine ring; --OCH 2 SCH 2 O--; --OS(═O)O--; --OC(═O)O--; --OCH 2 O--; --OC(═S)O--; --OC(═O)C(═O)O--; --OC(CH 3 ) 2 O--; --OC((CH 2 ) 3 NH 2 )(CH 3 )O--; --OC(OCH 3 )(CH 2 CH 2 CH 3 )O--; --OS(═O)O--; --NHC(═O)NH--; --OC(═O)NH--; --NHC(═O)O--; --NHCH 2 O--; --OCH 2 NH--; --NHC(═SO--; --OS (═O)NH--; --NHC(═O)C(═O)O--; --OC(═O)C(═O)NH--; --NHC(═O)C(═O)NH--; --OC(CH 3 ) 2 O--; --NHC(CH 3 ) 2 O--; --OC(CH 3 ) 2 NH-- or any group that, when administered to a mammalian subject, cleaves to form a free dihydroxyl or diamino or hydroxyl and amino; R 5a is selected from hydrogen, halogen, C 1 -C 6 alkyl, --N(R 20 ) 2 , --SR 20 , or --OR 20 ; R 6a is selected from: hydrogen, halogen, C 1 -C 6 alkyl, --N(R 20 ) 2 , --SR 20 or --OR 21 ; R 5 and R 5a can alternatively join to form ═O, ═S, or a ketal ring; R 6 and R 6a can alternatively join to form ═O, ═S, or a ketal ring; R 20 and R 21 are independently selected from: hydrogen; C 1 -C 6 alkyl substituted with 0-3 R 11 ; C 3 -C 6 alkoxyalkyl substituted with 0-3 R 11 ; C 1 -C 6 alkylcarbonyl substituted with 0-3 R 11 ; C 1 -C 6 alkoxycarbonyl substituted with 0-3 R 11 ; C 1 -C 6 alkylaminocarbonyl substituted with 0-3 R 11 ; benzoyl substituted with 0-3 R 12 ; phenoxycarbonyl substituted with 0-3 R 12 ; phenylaminocarbonyl substituted with 0-3 R 12 ; or any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl, amino or sulfhydryl; R 11 is selected from one or more of the following: H, keto, halogen, cyano, --CH 2 NR 13 R 1 , --NR 13 R 14 , --CO 2 R 13 , --OC(═O)R 13 , --OR 13 , C 2 -C 6 alkoxyalkyl, --S(O) m R 13 , --NHC(═NH)NHR 13 , --C(═NH)NHR 13 , --C(═O)NR 13 R 14 , --NR 14 C(═O)R 13 , ═NOR 14 , --NR 14 C(═O)OR 14 , --OC(═O)NR 13 R 14 , --NR 13 C(═O)NR 13 R 14 , --NR 14 SO 2 NR 13 R 14 , --NR 14 SO 2 R 13 , --SO 2 NR 13 R 14 , --OP(O)(OR 13 ) 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 3 -C 10 cycloalkyl, C 3 -C 6 cycloalkylmethyl, benzyl, phenethyl, phenoxy, benzyloxy, nitro, C 7 -C 10 arylalkyl, hydroxamic acid, hydrazide, boronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, C 1 -C 4 alkyl substituted with --NR 13 R 14 , C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, pyridylcarbonyloxy, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --OCH 2 CO 2 H, 2-(1-morpholino)ethoxy, azido, or --(R 14 )═N(OR 14 ); -- 3amino acids linked together via amide bonds, said amino acid being linked via the amine or carboxylate terminus; C 3 -C 10 cycloalkyl substituted with 0-2 R 12 ; C 1 -C 4 alkyl substitued with 0-2 R 12 aryl(C 1 -C 3 alkyl) substituted with 0-2 R 12 ; C 2 -C 6 alkoxyalkyl, substituted with 0-2 R 12 ; C 1 -C 4 alkylcarbonyloxy substituted with 0-2 R 12 , C 6 -C 10 arylcarbonyloxy substituted with 0-2 R 12 , a C 5 -C 14 carbocyclic residue substituted with 0-3 R 12 ; or a 5-to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-3 R 12 ; R 11A is selected from one or more of the following: H, keto, halogen, cyano, --CH 2 NH 2 , --NH 2 , --NHMe, --CO 2 H, --OC(═O)(C 1 -C 3 alkyl), --OH, C 2 -C 6 alkoxyalkyl, --C(═O)NH 2 , --OC(═O)NH 2 , --NHC(═O)NH 2 , --SO 2 NH 2 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 3 -C 10 cycloalkyl, C 3 -C 6 cycloalkylmethyl, benzyl, phenethyl, phenoxy, benzyloxy, nitro, C 7 -C 10 arylalkyl, hydroxamic acid, hydrazide, boronic acid, C 3 -C 6 cycloalkoxy, C 1 -C 4 alkyl substituted with --NH 2 , C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --OCH 2 CO 2 H, 2-(1-morpholino)ethoxy, azido, aryl(C 1 -C 3 alkyl), a C 5 -C 14 carbocyclic residue; a 5-to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system substituted with 0-3 R 12A ; R 12 , when a substituent on carbon, is selected from one or more of the following: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, C 7 -C 10 arylalkyl, C 1 -C 4 alkoxy, --CO 2 H, hydroxamic acid, hydrazide, oronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, --OR 13 , C 1 -C 4 alkyl substituted with --NR 13 R 14 , --NR 13 R 14 , C 2 -C 6 alkoxyalkyl optionally substituted with --Si(CH 3 ) 3 ,, Cl--C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --S(O) m R 13 , --SO 2 NR 13 R 14 , --NHSO 2 R 14 , --OCH 2 CO 2 R 13 , 2-(1-morpholino)ethoxy, or --C(R 14 )═N(OR 14 ); or a 5-or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur; or R 12 may be a 3-or 4-carbon chain attached to adjacent carbons on the ring to form a fused 5-or 6-membered ring, said 5-or 6-membered ring being optionally substituted on the aliphatic carbons with halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, or --NR 13 R 14 ; or, when R 12 is attached to a saturated carbon atom, it may be ═O or ═S; or when R 12 is attached to sulfur it may be ═O; R 12 , when a substituent on nitrogen, is selected from one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, --CH 2 NR 13 R 14 , --NR 13 R 14 , C 2 -C 6 alkoxyalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxycarbonyl, --CO 2 H, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, or --C(R 14 )═N(OR 14 ); R 12A , when a substituent on carbon, is selected from one or more of the following: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, C 7 -C 10 arylalkyl, C 1 -C 4 alkoxy, --CO 2 H, hydroxamic acid, hydrazide, boronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, --OR 13 , C 1 -C 4 alkyl substituted with --NH 2 , --NH 2 , --NHMe, C 2 -C 6 alkoxyalkyl optionally substituted with --Si(CH 3 ) 3 , C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --S(O) m Me, --SO 2 NH 2 , --NHSO 2 Me, --OCH 2 CO 2 R 13 , 2-(1-morpholino)ethoxy, --C(═NOH)NH 2 ; or a 5-or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur; or R 12A may be a 3-or 4-carbon chain attached to adjacent carbons on the ring to form a fused 5-or 6-membered ring, said 5-or 6-membered ring being optionally substituted on the aliphatic carbons with halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, or --NH 2 ; or, when R 12A is attached to a saturated carbon atom or sulfur, it may be ═O or ═S; R 12A , when a substituent on nitrogen, is selected from one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, --CH 2 NH 2 , --NH 2 , C 2 -C 6 alkoxyalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxycarbonyl, --CO 2 H, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, --C(═NOH)NH 2 ; R 13 is selected from: H; phenyl substituted with 0-3 R 11A ; benzyl substituted with 0-3 R 11A ; C 1 -C 6 alkyl substituted with 0-3 R 11A ; C 2 -C 4 alkenyl substituted with 0-3 R 11A ; C 1 -C 6 alkylcarbonyl substituted with 0-3 R 11A ; C 1 -C 6 alkoxycarbonyl substituted with 0-3 R 11A ; C 1 -C 6 alkylaminocarbonyl substituted with 0-3 R 11A ; C 3 -C 6 alkoxyalkyl substituted with 0-3 R 11A ; an amine protecting group when R 13 is bonded to N; or a hydroxy protecting group when R 13 is bonded to O; R 14 is hydrogen, hydroxy, CF 3 ; C 1 -C 6 alkyl substituted with 0-3 groups selected from OH, C 1 -C 4 alkoxy, halogen, NH 2 , C 1 -C 6 alkoxy; NH 2 ; --NH(C 1 -C 4 alkyl), C 2 -C 6 alkenyl; phenyl, benzyl, an amine protecting group when R 14 is bonded to N, or a hydroxy protecting group when R 14 is bonded to O; R 13 and R 14 can alternatively join to form --(CH 2 ) 4 --, --(CH 2 ) 5 --, --CH 2 CH 2 N(R 15 )CH 2 CH 2 --, or --CH 2 CH 2 OCH 2 CH 2 --; R 15 is H or CH 3 ; m is 0, 1 or 2; W is --N(R 22 )C(═Z)N(R 23 )--; wherein: Z is O; R 22 and R 23 are independently selected from the following: hydrogen; C 1 -C 8 alkyl substituted with 0-3 R 31 ; C 2 -C 8 alkenyl substituted with 0-3 R 31 ; C 2 -C 8 alkynyl substituted with 0-3 R 31 ; a C 3 -C 14 carbocyclic ring system substituted with 0-5 R 31 or R 32 ; a 5-to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-5 R 32 ; --OR 22a ; or --N(R 22a )(R 22b ); R 22a and R 22b are independently selected from the following: hydrogen; C 1 -C 8 alkyl substituted with 0-3 R 31 ; C 2 -C 8 alkenyl substituted with 0-3 R 31 ; C 2 -C 8 alkynyl substituted with 0-3 R 31 ; a C 3 -C 14 carbocyclic ring system substituted with 0-5 R 31 or R 32 ; a 5-to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-5 R 32 ; alternatively, R 22 can join with R 4 or R 4A to form a 5-or 6-membered fused heterocyclic ring or carbocyclic ring substituted with 0-2 R 12 , said heterocyclic ring containing 1-3 heteroatoms independently selected from N, S, or O; or alternatively, R 23 can join with R 7 or R 7A to form a 5-or 6-membered fused heterocyclic ring or carbocyclic ring substituted with 0-2 R 12 , said heterocyclic ring containing 1-3 heteroatoms independently selected from N, S, or O; or alternatively, R 22 or R 23 can join with R 5 or R 6 to form a 0- to 7-membered bridge to form a carbocyclic or heterocyclic ring, said bridge being substituted with 0-2 R 12 and said bridge containing 0-3 heteroatoms independently selected from N, S, or O (i.e., a O-membered bridge is formed when R 22 or R 23 are taken together with R 5 or R 6 to form a direct bond); or alternatively R23 can join with R7A to form a direct bond; or alternatively R22 can join with R4A to form a direct bond; R 31 is selected from one or more of the following: keto, halogen, cyano, --CH 2 NR 13 R 14 , --NR 13 R 14 , --CO 2 R 13 , --C(═O)R 11 , --OC(═O)R 13 , --OR 13 , C 2 -C 6 alkoxyalkyl, --S(O) m R 13 , --NHC(═NH)NHR 13 , --C(═NH)NHR 13 , --C(═O)NR 13 R 14 , --NR 14 C(═O)R 13 , ═NOR 14 , --NR 14 C(═O)OR 14 , --OC(═O)NR 13 R 14 , --NR 13 C(═O)NR 13 R 14 --NR 13 C(═S)NR 13 R 14 , --NR 14 SO 2 NR 13 R 14 , --NR 14 SO 2 R 13 , --SO 2 NR 13 R 14 , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 3 -C 10 cycloalkyl, C 3 -C 6 cycloalkylmethyl, benzyl, phenethyl, phenoxy, benzyloxy, nitro, C 7 -C 10 arylalkyl, hydroxamic acid, hydrazide, oxime, boronic acid, sulfonamide, formyl, C 3 -C 6 cycloalkoxy, C 1 -C 4 alkyl substituted with --NR 13 R 14 , C 1 -C 4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkylcarbonylamino, --OCH 2 CO 2 R 13 , 2-(1-morpholino)ethoxy, azido, --C(R 14 )═N(OR 14 ); or - 3amino acids, linked together via amide bonds, said amino acid being linked via the amine or carboxylate terminus; a C 5 -C 14 carbocyclic residue substituted with 0-5 R 32 ; or a 5-to 10-membered heterocyclic ring system containing 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, said heterocyclic ring system being substituted with 0-2 R 32 ; R 32 , when a substituent on carbon, is selected from one or more of the following: phenethyl, phenoxy, C 3 -C 10 cycloalkyl, C 3 -C 6 cycloalkylmethyl, C 7 -C 10 arylalkyl, hydrazide, oxime, boronic acid, C 2 -C 6 alkoxyalkyl, methylenedioxy, ethylenedioxy, C 1 -C 4 alkylcarbonyloxy, --NHSO 2 R 14 , benzyloxy, halogen, 2-(1 -morpholino)ethoxy, --CO 2 R 13 , hydroxamic acid, --CONR 13 NR 13 R 14 , cyano, boronic acid, sulfonamide, --CHO, C 3 -C 6 cycloalkoxy, --NR 13 R 14 , --C(R 14 )═N(OR 14 ), NO 2 , --OR 13 , --NR 40 R 41 , --SO m R 13 , --SO m NR 13 R 14 , --C(═O)NR 13 R 14 , --OC(═O)NR 13 R 14 , --C(═O)R 11 , --OC(═O)R 11 , --OCO 2 R 13 , phenyl, --C(═O)NR 13 --(C 1 -C 4 alkyl)-NR 13 R 14 , --C(═O)NR 40 R 41 , C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 2 -C 4 haloalkenyl, C 1 -C 4 haloalkynyl, or --C(═O)NR 13 C(R 11 ) 2 NR 13 R 14 ; --C(═O)NR 13 C(R 11 ) 2 NR 13 NR 11 ; --C(═O)NR 13 C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O)NR 13 -(C 1 -C 4 alkyl)--NR 13 CO 2 R 13 ; --C(═O)N(R 13 )-(C 1 -C 4 alkyl)-R 11 ; or --C(═O)C(R 11 ) 2 NR 13 R 11 ; --C(═O)C(R 11 ) 2 NR 13 NR 11 ; --C(═O)C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O)(C 1 -C 4 alkyl)--NR 13 R 14 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 CO 2 R 13 ; or C 1 -C 4 alkoxy substituted with 0-4 groups selected from: R 11 , C 3 -C 6 cycloalkyl, --CO 2 R 13 , --C(═O)NR 13 R 14 , --NR 13 R 14 or OH; C 1 -C 4 alkyl substituted with 0-4 groups selected from: R 11 , ═NR 14 , ═NNR 13 C(═O)NR 13 R 14 or --N 13 R 14 , ═NNR 13 C(═O)OR 13 ,; C 2 -C 4 alkenyl substituted with 0-4 R 11 ; C 2 -C 4 alkynyl substituted with 0-4 R 11 ; a 5- or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen or sulfur, substituted with 0-2 R 12 ; or R 32 may be a 3- or 4-carbon chain attached to adjacent carbons on the ring to form a fused 5-or 6-membered ring, said 5- or 6-membered ring being optionally substituted on the aliphatic carbons with halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, or --NR 13 R 14 ; or, when R 32 is attached to a saturated carbon atom, it may be ═O or ═S, ═NOH; or when R 32 is attached to sulfur it may be ═O. R 32 , when a substituent on nitrogen, is selected from one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, --CH 2 NR 13 R 14 , --NR 13 R 14 , C 2 -C 6 alkoxyalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxycarbonyl, --CO 2 H, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonyl, or --C(R 14 )═N(OR 14 ); C 1 -C 6 alkyl substituted with 0-3 R 11 ; hydroxyl; C 1 -C 6 alkoxy substituted with 0-3 R 11 or --NR 38 R 39 ; R 38 and R 39 are independently selected from: hydrogen; C 1 -C 6 alkyl substituted with 0-3 R 11 or an amine protecting groug;] R 40 is selected from: H or C 1 -C 3 alkyl; R 41 is selected from: --C(═O)NR 13 R 14 ; --C(═O)NR 13 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 NR 13 R 14 ; --C(═O)C(R 11 ) 2 NR 13 CO 2 R 13 ; --C(═O)H; --C(═O)R 11 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 R 14 ; --C(═O)-(C 1 -C 4 alkyl)--NR 13 CO 2 R 13 ; - 3amino acids linked together via amide bonds, and linked to the N atom via the carboxylate terminus; provided that: R 4 , R 4A , R 7 and R 7A are not all hydrogen; when R 4 , R 4A are hydrogen, R 22 is not hydrogen; and (b) a vehicle comprising a fatty acid ester of glycerol, a fatty acid ester of polyethylene glycol, or mixture thereof, wherein said vehicle has a hydrophil-lipophil balance of at least about 10.
41. A pharmaceutical dosage form of claim 40 wherein said compound of Formula (I)is present in an amount of about 50-250 mg/capsule.Join the waitlist — get patent alerts
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